The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid repro...The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.展开更多
The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitabl...The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew （Tupaia belangeri） aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database （www.treeshrewdb.org） has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 （HSV-1） and hepatitis C virus （HCV） infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.展开更多
Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body...Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low-cost of maintenance, tree shrew has been proposed to be an alternative experimental animal to primates in biomedical research. However, there are some debates regarding the exact phylogenetic affinity of tree shrew to primates. In this study, we determined the mtDNA entire genomes of three Chinese tree shrews （T. belangeri chinensis） and one Malayan flying lemur （Galeopterus variegatus）. Combined with the published data for species in Euarchonta, we intended to diseen] the phylogenetic relationship among representative species of Dermoptera, Scandentia and Primates. The mtDNA genomes of Chinese tree shrews and Malayan flying lemur shared similar gene organization and structure with those of other mammals. Phylogenetic analysis based on 12 concatenated mitochondrial proteinencoding genes revealed a closer relationship between species of Scandentia and Glires, whereas species of Dermoptera were clustered with Primates. This pattern was consistent with previously reported phylogeny based on mtDNA data, but differed from the one reconstructed on the basis of nuclear genes. Our result suggested that the matrilineal affinity of tree shrew to primates may not be as close as we had thought. The ongoing project for sequencing the entire genome of Chinese tree shrew will provide more information to clarify this important issue.展开更多
Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depres...Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstr展开更多
Valid animal models are useful for studying the pathophysiology of specific disorders,such as neural disease,diabetes and cancer.Previous molecular phylogeny studies indicate that the tree shrew is in the same order a...Valid animal models are useful for studying the pathophysiology of specific disorders,such as neural disease,diabetes and cancer.Previous molecular phylogeny studies indicate that the tree shrew is in the same order as(or a close sister to)primates,and thus may be an ideal model in which to study human disease.In this study,the proteome of liver and muscle tissue in tree the shrew was identified by combining peptide fractionation and LC-MS/MS identification.In total,2146 proteins were detected,including 1759 proteins in liver samples and 885 proteins in skeletal muscle samples from the tree shrew.Further sub-source analysis revealed that nearly half of the identified proteins(846 proteins and 418 proteins)were derived from human database.In this study,we are the first to describe the characteristics of the proteome from the liver and skeletal muscle of the tree shrew.Phylogenetic tree analysis based on these proteomic data showed that the tree shrew is closer to primates(human)than to glires(the mouse and rat).展开更多
Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolution...Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.展开更多
Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and ...Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.展开更多
Animal models are essential for the development of new anti-infectious drugs.Although some bacterial infection models have been established in rodents,small primate models are rare.Here,we report on two bacterial infe...Animal models are essential for the development of new anti-infectious drugs.Although some bacterial infection models have been established in rodents,small primate models are rare.Here,we report on two bacterial infection models established in tree shrew（Tupaia belangeri chinensis）.A burnt skin infection model was induced by dropping 5×106 CFU of Staphylococcus aureus on the surface of a wound after a third degree burn.This dose of S.aureus caused persistent infection for 7 days and obvious inflammatory response was observed 4 days after inoculation.A Dacron graft infection model,2×106 CFU of Pseudomonas aeruginosa also caused persistent infection for 6 days,with large amounts of pus observed 3 days after inoculation.These models were used to evaluate the efficacy of levofloxacin（LEV） and cefoperazone（CPZ）,which reduced the viable bacteria in skin to 4log10 and 5log10 CFU/100 mg tissue,respectively.The number of bacteria in graft was significantly reduced by 4log10 CFU/mL treatment compared to the untreated group（P0.05）.These results suggest that two bacterial infection models were successfully established in tree shrew using P.aeruginosa and S.aureus.In addition,tree shrew was susceptible to P.aeruginosa and S.aureus,thus making it an ideal bacterial infection animal model for the evaluation of new antimicrobials.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis)is emerging as an important experimental animal in multiple fields of biomedical research.Comprehensive reference genome annotation for both mRNA and long non-coding R...The Chinese tree shrew(Tupaia belangeri chinensis)is emerging as an important experimental animal in multiple fields of biomedical research.Comprehensive reference genome annotation for both mRNA and long non-coding RNA(lncRNA)is crucial for developing animal models using this species.In the current study,we collected a total of 234 high-quality RNA sequencing(RNA-seq)datasets and two long-read isoform sequencing(ISO-seq)datasets and improved the annotation of our previously assembled high-quality chromosomelevel tree shrew genome.We obtained a total of 3514 newly annotated coding genes and 50576 lncRNA genes.We also characterized the tissuespecific expression patterns and alternative splicing patterns of mRNAs and lncRNAs and mapped the orthologous relationships among 11 mammalian species using the current annotated genome.We identified 144 tree shrew-specific gene families,including interleukin 6(IL6)and STT3 oligosaccharyltransferase complex catalytic subunit B(STT3B),which underwent significant changes in size.Comparison of the overall expression patterns in tissues and pathways across four species(human,rhesus monkey,tree shrew,and mouse)indicated that tree shrews are more similar to primates than to mice at the tissue-transcriptome level.Notably,the newly annotated purine rich element binding protein A(PURA)gene and the STT3B gene family showed dysregulation upon viral infection.The updated version of the tree shrew genome annotation(KIZ version 3:TS_3.0)is available at http://www.treeshrewdb.org and provides an essential reference for basic and biomedical studies using tree shrew animal models.展开更多
A new species of white-toothed shrew,Crocidura anhuiensis Zhang,Zhang&Li,sp.nov.is described from Mount Huang,China.Genetic sequence(mt DNA Cyt b gene)and morphological(external and skull)data are used to distingu...A new species of white-toothed shrew,Crocidura anhuiensis Zhang,Zhang&Li,sp.nov.is described from Mount Huang,China.Genetic sequence(mt DNA Cyt b gene)and morphological(external and skull)data are used to distinguish this newly discovered species.The phylogenetic analysis shows that the materials of this work are monophyletic and allied to C.attenuata by the uncorrected genetic distance 4.9–5.1%,which suggests a species-level divergence.Morphologically,the materials are different from C.attenuata by presenting a greater proportion of tail-to-body ratio and the presence of an obvious tooth root in the mandible.Based on those data,the unnamed species is described as a new species which is currently known only from the Wild Monkey Valley,Mount Huang,Anhui Province,China.展开更多
Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been wi...Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been widely used for pre-clinical studies due to their small size,clear genetic backgrounds,rapid propagation,and mature transgenic technologies.However,because rodents are evolutionarily distinct from humans,many pre-clinical research results using rodent models cannot be reproduced in the clinic.Non-human primates（NHPs） may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution,immune system,physiology and metabolism.This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens.Finally,future research directions for the use of NHPs in cancer research are discussed.展开更多
Diffusion-weighted magnetic resonance imaging（d MRI） is widely used to study white and gray matter（GM） micro-organization and structural connectivity in the brain. Super-resolution track-density imaging（TDI） is ...Diffusion-weighted magnetic resonance imaging（d MRI） is widely used to study white and gray matter（GM） micro-organization and structural connectivity in the brain. Super-resolution track-density imaging（TDI） is an image reconstruction method for d MRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI（st TDI）, a variation of TDI with enhanced contrast for GM structures, to reconstruct directionencoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging（DTI） method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with st TDI,but not with DTI reconstructions from the same d MRI data.The possible mechanisms underlying the enhanced GM contrast are discussed.展开更多
In this study, a new species of white-toothed shrew, Crocidura huangshanensis Yang, BW Zhang & Li, sp. nov. was described based on five individuals collected from the Mt. Huang of China. Its morphological data and...In this study, a new species of white-toothed shrew, Crocidura huangshanensis Yang, BW Zhang & Li, sp. nov. was described based on five individuals collected from the Mt. Huang of China. Its morphological data and mt DNA sequences(Cyt b) were analyzed. Morphologically, C. huangshanensis Yang, BW Zhang & Li, sp. nov. is different from its congeners(C. anhuiensis and C. attenuata) by the body and skull smaller in size and the premolar and molar smoother, which are also different from other Southeast Asian Crocidura. The phylogenetic analysis shows that all individuals of C. huangshanensis Yang, BW Zhang & Li, sp. nov. merged into a single clade. In addition, the genetic distance between C. huangshanensis Yang, BW Zhang & Li, sp. nov. and other species of Crocidura is ranged from 9.8% to 15.3%, indicating a species-level divergence. The new species is currently distributed in the Wild Monkey Valley, located in Mt. Huang, China.展开更多
Endosymbionts influence many aspects of their hosts’ health conditions, including physiology, development, immunity, metabolism, etc. Tree shrews(Tupaia belangeri chinensis) have attracted increasing attention in mod...Endosymbionts influence many aspects of their hosts’ health conditions, including physiology, development, immunity, metabolism, etc. Tree shrews(Tupaia belangeri chinensis) have attracted increasing attention in modeling human diseases and therapeutic responses due to their close relationship with primates. To clarify the situation of symbiotic bacteria from their body surface, oral cavity, and anus, 12 wild and 12 the third generation of captive tree shrews were examined. Based on morphological and cultural characteristics, physiological and biochemical tests, as well as the 16 S rDNA full sequence analysis, 12 bacteria strains were isolated and identified from the wild tree shrews: body surface: Bacillus subtilis(detection rate 42%), Pseudomonas aeruginosa(25%), Staphlococcus aureus(33%), S. Epidermidis(75%), Micrococcus luteus(25%), Kurthia gibsonii(17%); oral cavity: Neisseria mucosa(58%), Streptococcus pneumonia(17%); anus: Enterococcus faecalis(17%), Lactococus lactis(33%), Escherichia coli(92%), Salmonella typhosa(17%); whereas, four were indentified from the third generation captive tree shrews: body surface: S. epidermidis(75%); oral cavity: N.mucosa(67%); anus: L. lactis(33%), E. coli(100%). These results indicate that S. epidermidis, N. mucosa, L. lactis and E. coli were major bacteria in tree shrews, whereas, S. aureus, M. luteus, K. gibsonii, E. faecalis and S. typhosa were species-specific flora. This study facilitates the future use of tree shrews as a standard experimental animal and improves our understanding of the relationship between endosymbionts and their hosts.展开更多
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hm...Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.展开更多
Basal cell carcinoma （BCC） is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog （Hh）...Basal cell carcinoma （BCC） is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog （Hh） signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews （Tupaia belangeri chinensis） are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened （Smo） used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lenUviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future展开更多
Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of fe...Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.展开更多
As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveill...As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained （conception rate=74%）. Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.展开更多
基金supported by the National Nature Science Foundation of China(81325016,U1602221,81322038 and U1502222)
文摘The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.
基金supported by the grant of the National Natural Science Foundation of China(NSFC U1402224)the Chinese Academy of Sciences(CAS zsys-02)
文摘The Chinese tree shrew （Tupaia belangeri chinensis） a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew （Tupaia belangeri） aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database （www.treeshrewdb.org） has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 （HSV-1） and hepatitis C virus （HCV） infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.
基金supported by grants from Chinese Academy of Sciences (Nos.KSCX2-EW-R-11 and KSCX2-EW-J-23)the National 863 Project of China (No.2012AA021801)Yunnan Province (No.2009CI119)
文摘Tree shrew （Tupaia belangeri） is currently placed in Order Scandentia and has a wide distribution in Southeast Asia and Southwest China. Due to its unique characteristics, such as small body size, high brain-to-body mass ratio, short reproductive cycle and life span, and low-cost of maintenance, tree shrew has been proposed to be an alternative experimental animal to primates in biomedical research. However, there are some debates regarding the exact phylogenetic affinity of tree shrew to primates. In this study, we determined the mtDNA entire genomes of three Chinese tree shrews （T. belangeri chinensis） and one Malayan flying lemur （Galeopterus variegatus）. Combined with the published data for species in Euarchonta, we intended to diseen] the phylogenetic relationship among representative species of Dermoptera, Scandentia and Primates. The mtDNA genomes of Chinese tree shrews and Malayan flying lemur shared similar gene organization and structure with those of other mammals. Phylogenetic analysis based on 12 concatenated mitochondrial proteinencoding genes revealed a closer relationship between species of Scandentia and Glires, whereas species of Dermoptera were clustered with Primates. This pattern was consistent with previously reported phylogeny based on mtDNA data, but differed from the one reconstructed on the basis of nuclear genes. Our result suggested that the matrilineal affinity of tree shrew to primates may not be as close as we had thought. The ongoing project for sequencing the entire genome of Chinese tree shrew will provide more information to clarify this important issue.
基金supported by grants KSCX2-EW-R-12 and KSCX2-EW-J-23 from the Chinese Academy of Sciences
文摘Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstr
基金supported by the grants from the Knowledge Innovation Program of the Chinese Academy of Sciences(No.KSCX2-EW-R-12)grants from National Natural Science Foundation Youth Fund of China(Grant No.30900261)the Support of SA-SIBS Scholarship Program.
文摘Valid animal models are useful for studying the pathophysiology of specific disorders,such as neural disease,diabetes and cancer.Previous molecular phylogeny studies indicate that the tree shrew is in the same order as(or a close sister to)primates,and thus may be an ideal model in which to study human disease.In this study,the proteome of liver and muscle tissue in tree the shrew was identified by combining peptide fractionation and LC-MS/MS identification.In total,2146 proteins were detected,including 1759 proteins in liver samples and 885 proteins in skeletal muscle samples from the tree shrew.Further sub-source analysis revealed that nearly half of the identified proteins(846 proteins and 418 proteins)were derived from human database.In this study,we are the first to describe the characteristics of the proteome from the liver and skeletal muscle of the tree shrew.Phylogenetic tree analysis based on these proteomic data showed that the tree shrew is closer to primates(human)than to glires(the mouse and rat).
基金Yunnan Province High-Profile Talent Project (2010CI114)the Chinese Academy of Sciences,Basic Frontier Project (KSCX2-EW-J-23)
文摘Breast cancer is a common malignant tumor.It is essential to develop suitable animal models for discovering novel preventive and therapeutic approaches.Tree shrews（Tupaia belangeri chinensis） have a closer evolutionary relationship with humans than do rodents,which have been widely used in laboratory research.Spontaneous breast tumors were identified in tree shrews in 1960s;however,no detailed studies about tree shrew breast tumors have been conducted to date.Here,we characterized a spontaneous breast tumor from tree shrews by Haematoxylin Eosin（HE） staining.This tumor was identified as a papillary tumor.Immunohistochemical staining（IHC） for progesterone receptor（PR）,Ki-67 and cleaved caspase-3 showed that tumor cells were positive for PR,highly proliferative,and less apoptotic compared to normal breast epithelial cells.Thus,the spontaneous tumor of tree shrew is very close to human papillary tumors in terms of morphology and pathology and we concluded that tree shrew may be a suitable animal model for breast cancer research.
基金supported by the National High-Tech R&D Program(2014ZX09102042)the National Natural Science Foundation of China(81373142)the Natural Science Foundation of Yunnan Province(2012ZA009)
文摘Coxsackie virus A16(CA16) is commonly recognized as one of the main human pathogens of hand-foot-mouth disease(HFMD). The clinical manifestations of HFMD include vesicles of hand, foot and mouth in young children and severe inflammatory CNS lesions. In this study, experimentally CA16 infected tree shrews(Tupaia belangeri) were used to investigate CA16 pathogenesis. The results showed that both the body temperature and the percentages of blood neutrophilic granulocytes / monocytes of CA16 infected tree shrews increased at 4-7 days post infection. Dynamic distributions of CA16 in different tissues and stools were found at different infection stages. Moreover, the pathological changes in CNS and other organs were also observed. These findings indicate that tree shrews can be used as a viable animal model to study CA16 infection.
基金financially supported by the Project from the Chinese Academy of Sciences (KSCX2-EW-R-11)the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province (KSCX2-EW-J-23)Science and Technology Department of Yunnan Province (2011C1139)
文摘Animal models are essential for the development of new anti-infectious drugs.Although some bacterial infection models have been established in rodents,small primate models are rare.Here,we report on two bacterial infection models established in tree shrew（Tupaia belangeri chinensis）.A burnt skin infection model was induced by dropping 5×106 CFU of Staphylococcus aureus on the surface of a wound after a third degree burn.This dose of S.aureus caused persistent infection for 7 days and obvious inflammatory response was observed 4 days after inoculation.A Dacron graft infection model,2×106 CFU of Pseudomonas aeruginosa also caused persistent infection for 6 days,with large amounts of pus observed 3 days after inoculation.These models were used to evaluate the efficacy of levofloxacin（LEV） and cefoperazone（CPZ）,which reduced the viable bacteria in skin to 4log10 and 5log10 CFU/100 mg tissue,respectively.The number of bacteria in graft was significantly reduced by 4log10 CFU/mL treatment compared to the untreated group（P0.05）.These results suggest that two bacterial infection models were successfully established in tree shrew using P.aeruginosa and S.aureus.In addition,tree shrew was susceptible to P.aeruginosa and S.aureus,thus making it an ideal bacterial infection animal model for the evaluation of new antimicrobials.
基金This study was supported by the National Natural Science Foundation of China(U1902215 to Y.G.Y.and 31970542 to Y.F.)Chinese Academy of Sciences(Light of West China Program xbzg-zdsys-201909 to Y.G.Y.)Yunnan Province(202001AS070023 and 2018FB046 to D.D.Y.and 202002AA100007 to Y.G.Y.)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)is emerging as an important experimental animal in multiple fields of biomedical research.Comprehensive reference genome annotation for both mRNA and long non-coding RNA(lncRNA)is crucial for developing animal models using this species.In the current study,we collected a total of 234 high-quality RNA sequencing(RNA-seq)datasets and two long-read isoform sequencing(ISO-seq)datasets and improved the annotation of our previously assembled high-quality chromosomelevel tree shrew genome.We obtained a total of 3514 newly annotated coding genes and 50576 lncRNA genes.We also characterized the tissuespecific expression patterns and alternative splicing patterns of mRNAs and lncRNAs and mapped the orthologous relationships among 11 mammalian species using the current annotated genome.We identified 144 tree shrew-specific gene families,including interleukin 6(IL6)and STT3 oligosaccharyltransferase complex catalytic subunit B(STT3B),which underwent significant changes in size.Comparison of the overall expression patterns in tissues and pathways across four species(human,rhesus monkey,tree shrew,and mouse)indicated that tree shrews are more similar to primates than to mice at the tissue-transcriptome level.Notably,the newly annotated purine rich element binding protein A(PURA)gene and the STT3B gene family showed dysregulation upon viral infection.The updated version of the tree shrew genome annotation(KIZ version 3:TS_3.0)is available at http://www.treeshrewdb.org and provides an essential reference for basic and biomedical studies using tree shrew animal models.
基金supported by Biodiversity Survey,Observation and Assessment Program of Ministry of Ecology and Environment of ChinaAnhui Province Higher Education Revitalization Plan+1 种基金2014 Colleges and Universities Outstanding Youth Talent Support Program2017 Anhui Province Academic and Technical Leaders candidates(2017H130)
文摘A new species of white-toothed shrew,Crocidura anhuiensis Zhang,Zhang&Li,sp.nov.is described from Mount Huang,China.Genetic sequence(mt DNA Cyt b gene)and morphological(external and skull)data are used to distinguish this newly discovered species.The phylogenetic analysis shows that the materials of this work are monophyletic and allied to C.attenuata by the uncorrected genetic distance 4.9–5.1%,which suggests a species-level divergence.Morphologically,the materials are different from C.attenuata by presenting a greater proportion of tail-to-body ratio and the presence of an obvious tooth root in the mandible.Based on those data,the unnamed species is described as a new species which is currently known only from the Wild Monkey Valley,Mount Huang,Anhui Province,China.
基金supported in part by a grant from Yunnan Province High-Profile Talent Project 2010CI114grants from Chinese Academy of Sciences(Basic frontier project,KSCX2-EW-J-23)~~
文摘Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been widely used for pre-clinical studies due to their small size,clear genetic backgrounds,rapid propagation,and mature transgenic technologies.However,because rodents are evolutionarily distinct from humans,many pre-clinical research results using rodent models cannot be reproduced in the clinic.Non-human primates（NHPs） may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution,immune system,physiology and metabolism.This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens.Finally,future research directions for the use of NHPs in cancer research are discussed.
基金supported by grants from the National Basic Research Development Program of China (2011CB707800)the National Natural Science Foundation of China (21790390, 21790392, and 61371014)
文摘Diffusion-weighted magnetic resonance imaging（d MRI） is widely used to study white and gray matter（GM） micro-organization and structural connectivity in the brain. Super-resolution track-density imaging（TDI） is an image reconstruction method for d MRI data, which is capable of providing spatial resolution beyond the acquired data, as well as novel and meaningful anatomical contrast that cannot be obtained with conventional reconstruction methods. TDI has been used to reveal anatomical features in human and animal brains. In this study, we used short track TDI（st TDI）, a variation of TDI with enhanced contrast for GM structures, to reconstruct directionencoded color maps of fixed tree shrew brain. The results were compared with those obtained with the traditional diffusion tensor imaging（DTI） method. We demonstrated that fine microstructures in the tree shrew brain, such as Baillarger bands in the primary visual cortex and the longitudinal component of the mossy fibers within the hippocampal CA3 subfield, were observable with st TDI,but not with DTI reconstructions from the same d MRI data.The possible mechanisms underlying the enhanced GM contrast are discussed.
基金supported by Biodiversity Survey,Observation and Assessment Program of Ministry of Ecology and Environment of ChinaBasic Special Investigation Project of The Ministry of Science and Technology+2 种基金Anhui Province Higher Education Revitalization Plan2014 Colleges and Universities Outstanding Youth Talent Support Program2017 Anhui Province Academic and Technical Leaders candidates(2017H130)
文摘In this study, a new species of white-toothed shrew, Crocidura huangshanensis Yang, BW Zhang & Li, sp. nov. was described based on five individuals collected from the Mt. Huang of China. Its morphological data and mt DNA sequences(Cyt b) were analyzed. Morphologically, C. huangshanensis Yang, BW Zhang & Li, sp. nov. is different from its congeners(C. anhuiensis and C. attenuata) by the body and skull smaller in size and the premolar and molar smoother, which are also different from other Southeast Asian Crocidura. The phylogenetic analysis shows that all individuals of C. huangshanensis Yang, BW Zhang & Li, sp. nov. merged into a single clade. In addition, the genetic distance between C. huangshanensis Yang, BW Zhang & Li, sp. nov. and other species of Crocidura is ranged from 9.8% to 15.3%, indicating a species-level divergence. The new species is currently distributed in the Wild Monkey Valley, located in Mt. Huang, China.
基金This study was supported by the National 863 Project of China （2012AA021801） and the Project of Frontier Study of Foundation, CAS （KSCX2-EW-R-11, KSCX2-EW-J-23）
文摘Endosymbionts influence many aspects of their hosts’ health conditions, including physiology, development, immunity, metabolism, etc. Tree shrews(Tupaia belangeri chinensis) have attracted increasing attention in modeling human diseases and therapeutic responses due to their close relationship with primates. To clarify the situation of symbiotic bacteria from their body surface, oral cavity, and anus, 12 wild and 12 the third generation of captive tree shrews were examined. Based on morphological and cultural characteristics, physiological and biochemical tests, as well as the 16 S rDNA full sequence analysis, 12 bacteria strains were isolated and identified from the wild tree shrews: body surface: Bacillus subtilis(detection rate 42%), Pseudomonas aeruginosa(25%), Staphlococcus aureus(33%), S. Epidermidis(75%), Micrococcus luteus(25%), Kurthia gibsonii(17%); oral cavity: Neisseria mucosa(58%), Streptococcus pneumonia(17%); anus: Enterococcus faecalis(17%), Lactococus lactis(33%), Escherichia coli(92%), Salmonella typhosa(17%); whereas, four were indentified from the third generation captive tree shrews: body surface: S. epidermidis(75%); oral cavity: N.mucosa(67%); anus: L. lactis(33%), E. coli(100%). These results indicate that S. epidermidis, N. mucosa, L. lactis and E. coli were major bacteria in tree shrews, whereas, S. aureus, M. luteus, K. gibsonii, E. faecalis and S. typhosa were species-specific flora. This study facilitates the future use of tree shrews as a standard experimental animal and improves our understanding of the relationship between endosymbionts and their hosts.
基金supported by the Hundred-Talent Program of Chinese Academy of Sciences(Y4065411411100050210)to J.L.+3 种基金the National Natural Science Foundation of China(8147131391649119)to J.L.the National Natural Science Foundation of China(31260242 to)F.Lthe National Science and Technology Infrastructure Program(2014BAI01B01-04)to S.L.
文摘Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.
基金supported by the National Key Research and Development Program of China(2016YFA0100900)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+2 种基金the National Nature Science Foundation of China(U1502224,81672764)the Yunnan Applied Basic Research Projects(2014FA038,2016FA009,2014FB182)supported by the Chinese Academy of Sciences Western Light Program,Youth Innovation Promotion Association,CAS
文摘Basal cell carcinoma （BCC） is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog （Hh） signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews （Tupaia belangeri chinensis） are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened （Smo） used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lenUviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future
基金supported by grants from the Chinese Academy of Sciences (KSCX2-EW-R-12, KSCX2-EW-J-23)the National Natural Science Foundation of China (81171294)Shanghai Science & Technology Development Foundation(12140904200)
文摘Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 °C, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.
基金supported by the Breakthrough Project of Strategic Priority Program of the Chinese Academy of Sciences(XDB13000000)
文摘As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained （conception rate=74%）. Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.
