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Comparative transcriptome analysis between rhesus macaques(Macaca mulatta) and crab-eating macaques(M. fascicularis) 被引量:1
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作者 Yu-Xiang Mao Yamei Li +6 位作者 Zikun Yang Ning Xu Shilong Zhang Xuankai Wang Xiangyu Yang Qiang Sun Yafei Mao 《Zoological Research》 SCIE CSCD 2024年第2期299-310,共12页
Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as... Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics. 展开更多
关键词 Crab-eating macaques Rhesus macaques Comparative transcriptomics Biomedical models Nonhuman primates RNA-SEQ Duplicated genes
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In vitro and in vivo models of acute alcohol exposure 被引量:9
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作者 Angela Dolganiuc Gyongyi Szabo 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第10期1168-1177,共10页
Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute a... Alcohol abuse is a global problem due to the financial burden on society and the healthcare system. While the harmful health effects of chronic alcohol abuse are well established, more recent data suggest that acute alcohol consumption also affects human wellbeing. Thus, there is a need for research models in order to fully understand the effect of acute alcohol abuse on different body systems and organs. The present manuscript summarizes the interdisciplinary advantages and disadvantages of currently available human and non-human models of acute alcohol abuse, and identifi es their suitability for biomedical research. 展开更多
关键词 MODELS Acute alcohol abuse HUMAN Nonhuman PROGRESS
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Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans 被引量:7
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作者 Magdalini Tsintou Kyriakos Dalamagkas Nikos Makris 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第3期425-437,共13页
The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of ef... The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline. 展开更多
关键词 animal models central nervous system regeneration clinical translation exosomes hydrogels neural tissue engineering nonhuman PRIMATES spinal cord injury stem cells stroke
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Nonhuman primate models of focal cerebral ischemia 被引量:17
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作者 Jingjing Fan Yi Li +3 位作者 Xinyu Fu Lijuan Li Xiaoting Hao Shasha Li 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第2期321-328,共8页
Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested c... Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model. 展开更多
关键词 nerve regeneration stroke cerebral ischemia middle cerebral artery occlusion nonhuman primates model selection neural regeneration
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Local transgene expression and whole-body transgenesis to model brain diseases in nonhuman primate 被引量:2
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作者 Lucie Chansel-Debordeaux Erwan Bezard 《Animal Models and Experimental Medicine》 CSCD 2019年第1期9-17,共9页
Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used a... Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate. 展开更多
关键词 ANIMAL models NEUROSCIENCE nonhuman PRIMATES
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Hepatitis B virus lineages in mammalian hosts:Potential for bidirectional cross-species transmission 被引量:1
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作者 Cibele R Bonvicino Miguel A Moreira Marcelo A Soares 《World Journal of Gastroenterology》 SCIE CAS 2014年第24期7665-7674,共10页
The hepatitis B virus(HBV)is a cosmopolitan infectious agent currently affecting over 350 million people worldwide,presently accounting for more than two billion infections.In addition to man,other hepatitis virus str... The hepatitis B virus(HBV)is a cosmopolitan infectious agent currently affecting over 350 million people worldwide,presently accounting for more than two billion infections.In addition to man,other hepatitis virus strains infect species of several mammalian families of the Primates,Rodentia and Chiroptera orders,in addition to birds.The mounting evidence of HBV infection in African,Asian and neotropical primates draws attention to the potential crossspecies,zoonotic transmission of these viruses to man.Moreover,recent evidence also suggests the humans may also function as a source of viral infection to other mammals,particularly to domestic animals like poultry and swine.In this review,we list all evidence of HBV and HBVlike infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species. 展开更多
关键词 Hepatitis B Hepatitis B virus nonhuman host Cross-species transmission Hepatitis B virus
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Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates 被引量:1
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作者 Vladimir P Baklaushev Oleg V Durov +12 位作者 Vladimir A Kalsin Eugene V Gulaev Sergey V Kim Ilya L Gubskiy Veronika A Revkova Ekaterina M Samoilova Pavel A Melnikov Dzhina D Karal-Ogly Sergey V Orlov Alexander V Troitskiy Vladimir P Chekhonin Alexander V Averyanov Jan-Eric Ahlfors 《World Journal of Stem Cells》 SCIE 2021年第5期452-469,共18页
BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cell... BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes. 展开更多
关键词 Direct cell reprogramming Neural precursor cells Directly reprogrammed neural precursor cells Spinal cord injury Nonhuman primates Regenerative therapy Evoked potentials
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Endovascular middle cerebral arterial occlusion in a nonhuman primate model of chronic stroke
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作者 Qiang Wang Tong Zhang Chunyu Zhao Bin Du Feng Gao Mei Wen Weijian Jiang 《Neural Regeneration Research》 SCIE CAS CSCD 2011年第8期629-634,共6页
No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, ... No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke. 展开更多
关键词 nonhuman primate animal model cerebral infarction chronic phase endovascular occlusion neural regeneration
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Comparative evaluation of acute phase proteins by C-reactive protein(CRP)and serum amyloid A(SAA)in nonhuman primates and feline carnivores
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作者 Tohru Kimura 《Animal Diseases》 2022年第4期258-268,共11页
The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acu... The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals. 展开更多
关键词 Acute phase proteins C-reactive protein Feline carnivores Nonhuman primates Serum amyloid A Zoo animal
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Development of a unilateral ureteral obstruction model in cynomolgus monkeys
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作者 Linghong Huang Jia Ni +2 位作者 Tanika Duncan Zhizhan Song Timothy S.Johnson 《Animal Models and Experimental Medicine》 CSCD 2021年第4期359-368,共10页
Background:Chronic kidney disease(CKD)has a high global prevalence and large unmet need.Central to developing new CKD therapies are in vivo models in CKD.However,next-generation antibody,protein,and gene therapies are... Background:Chronic kidney disease(CKD)has a high global prevalence and large unmet need.Central to developing new CKD therapies are in vivo models in CKD.However,next-generation antibody,protein,and gene therapies are highly specific,meaning some do not cross-react with rodent targets.This complicates preclinical development,as established in vivo rodent models cannot be utilized unless tool therapeutics are also developed.Tool compounds can be difficult to develop and,if available,typically have different epitopes,sequences,and/or altered affinity,making it unclear how efficacious the lead therapeutic may be,or what dosing regimen to investigate.To address this,we aimed to develop a nonhuman primate model of CKD.Methods:In vivo rodent unilateral ureteral obstruction(UUO)models kidney fibrosis and is commonly used due to its rapidity,consistency,and ease.We describe translation of this model to the cynomolgus monkey,specifically optimizing the model duration to allow adequate time for assessment of novel therapeutics prior to the fibrotic plateau.Results:We demonstrated that disease developed more slowly in cynomolgus monkeys than in rodents post-UUO,with advanced fibrosis developing by 6 weeks.The tubulointerstitial fibrosis in cynomolgus monkeys was more consistent with human obstructive disease than in rodents,having a more aggressive tubular basement expansion and a higher fibroblast infiltration.The fibrosis was also associated with increased transglutaminase activity,consistent with that seen in patients with CKD.Conclusion:This cynomolgus monkey UUO model can be used to test potential human-specific therapeutics in kidney fibrosis. 展开更多
关键词 animal models FIBROSIS KIDNEY nonhuman primates TRANSGLUTAMINASE
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Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin
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作者 Zhengzhao Liu Ying Lu +4 位作者 Wenbao Hu Hidetaka Hara Yifan Dai Zhiming Cai Lisha Mou 《Animal Models and Experimental Medicine》 CSCD 2020年第1期79-86,共8页
Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs.There are serious side ... Backgrounds:Streptozotocin(STZ)-induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs.There are serious side effects of this method,including nausea,emesis,weight loss,liver damage,renal failure,and metabolic acidosis.In order to reduce the side effects,diabetic monkeys were induced using clinicalgrade STZ.However,clinical-grade STZ is not available in China.Here,we establised a method by using 100 mg/kg analytical-grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal.Methods:Three cynomolgus monkeys were used in this study.100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein.After the STZ administration,blood glucose levels were examined every 1 or 2 hours in the first 48 hours.Then,blood glucose levels were examined twice per day during the first week after the STZ injection.Insulin and C-peptide levels were measured by ELISA.Blood chemistry of hepatic and renal function tests were performed.Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays.Results:The stimulated C-peptide level(Intravenous glucose tolerance test)which is less than 0.5 ng/mL,the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model.No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection.Conclusion:In summary,we established a safe and reproducible STZ-induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes. 展开更多
关键词 ANALYTICAL GRADE DIABETIC model nonhuman PRIMATE STZ
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Relationship between Age and Neurogenesis in Old World Monkeys
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作者 Tarique D. Perera Arkadiy Yaretskiy +8 位作者 Anna V. Rozenboym Zeena Audi Cecilia Lipira Jean Tang Jeremy Hill Lakshmi Thirumangalakudi Daniel C. Lee Andrew J. Dwork Jeremy D. Coplan 《Neuroscience & Medicine》 2013年第3期172-180,共9页
Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown ... Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown to be one of its most potent regulators in mice. The mechanism for the decline in neurogenesis with age is thought to be related to age-dependent changes in local and systemic neuroendocrinology and neurochemistry, as well as internal changes to precursor cells that result in decreased reactivity to normal stimuli. Since most of the data about neurogenesis and age were established from rodent studies, we sought to study this relationship in nonhuman primates in five previously studied cohorts of bonnet monkeys (Macaca radiata). In the present study, we statistically analyze the relationship of age and hippocampal neurogenesis rates, as measured by the number of DCX expressing cells in the subgranular zone of the dentate gyrus in 71 subjects with ages ranging from 3.5 to 17 years. We observed a non-significant relationship between age and doublecortin for subjects less than nine years old (corresponding to young and full adulthood) but a linear significant decline for subjects 9 years or greater (middle age and senescence). In contrast to previous studies that show neurogenesis to decline linearly throughout the lifespan, this study shows that neurogenesis occurs steadily throughout adulthood and begins to decline in middle age in bonnet macaques. 展开更多
关键词 NEUROGENESIS Age MACACA Radiate Nonhuman PRIMATES
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Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging 被引量:9
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作者 REN ZhenHua WANG JiaYin +2 位作者 ZOU ChunLin GUAN YunQian ZHANG Yu Alex 《Science China(Life Sciences)》 SCIE CAS 2011年第11期981-987,共7页
Recently,transplantation of allogeneic and autologous cells has been used for regenerative medicine.A critical issue is monitoring migration and homing of transplanted cells,as well as engraftment efficiency and funct... Recently,transplantation of allogeneic and autologous cells has been used for regenerative medicine.A critical issue is monitoring migration and homing of transplanted cells,as well as engraftment efficiency and functional capability in vivo.Monitoring of superparamagnetic iron oxide(SPIO) particles by magnetic resonance imaging(MRI) has been used in animal models and clinical settings to track labeled cells.A major limitation of MRI is that the signals do not show biological characteristics of transplanted cells in vivo.Bone marrow mesenchymal stem cells(MSCs) have been extensively investigated for their various therapeutic properties,and exhibit the potential to differentiate into cells of diverse lineages.In this study,cynomolgus monkey MSCs(cMSCs) were labeled with Molday ION Rhodamine-BTM(MIRB),a new SPIO agent,to investigate and characterize the biophysical and MRI properties of labeled cMSCs in vitro and in vivo.The results indicate that MIRB is biocompatible and useful for cMSCs labeling and cell tracking by multimodality imaging.Our method is helpful for detection of transplanted stem cells in vivo,which is required for understanding mechanisms of cell therapy. 展开更多
关键词 bone marrow mesenchymal stem cells MRI Molday ION Rhodamine-BTM TRANSPLANTATION nonhuman primate
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Detection of social group instability among captive rhesus macaques using joint network modeling 被引量:6
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作者 Brianne A. BEISNER Jian JIN +1 位作者 Hsieh FUSHING Brenda MCCOWAN 《Current Zoology》 SCIE CAS CSCD 2015年第1期70-84,共15页
Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We... Social stability in group-living animals is an emergent property which arises from the interaction amongst multiple behavioral networks. However, pinpointing when a social group is at risk of collapse is difficult. We used a joint network model- ing approach to examine the interdependencies between two behavioral networks, aggression and status signaling, from four sta- ble and three unstable groups of rhesus macaques in order to identify characteristic patterns of network interdependence in stable groups that are readily distinguishable from unstable groups. Our results showed that the most prominent source of aggres- sion-status network interdependence in stable social groups came from more frequent dyads than expected with opposite direc- tion status-aggression (i.e. A threatens B and B signals acceptance of subordinate status). In contrast, unstable groups showed a decrease in opposite direction aggression-status dyads (but remained higher than expected) as well as more frequent than ex- pected dyads with bidirectional aggression. These results demonstrate that not only was the stable joint relationship between ag- gression and status networks readily distinguishable from unstable time points, social instability manifested in at least two differ- ent ways. In sum, our joint modeling approach may prove useful in quantifying and monitoring the complex social dynamics of any wild or captive social system, as all social systems are composed of multiple interconnected networks [Current Zoology 61 (1): 70-84, 2015]. 展开更多
关键词 Nonhuman primates Network stability Social network analysis DOMINANCE AGGRESSION Status signaling
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Induction of core symptoms of autism spectrum disorder by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys 被引量:7
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作者 Shi-Hao Wu Xiao Li +13 位作者 Dong-Dong Qin Lin-Heng Zhang Tian-Lin Cheng Zhi-Fang Chen Bin-Bin Nie Xiao-Feng Ren Jing Wu Wen-Chao Wang Ying-Zhou Hu Yi-Lin Gu Long-Bao Lv Yong Yin Xin-Tian Hu Zi-Long Qiu 《Science Bulletin》 SCIE EI CSCD 2021年第9期937-946,M0004,共11页
Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders,whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to... Although CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders,whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined.Here we induced genetic mutations in MECP2,a critical gene linked to Rett syndrome(RTT)and autism spectrum disorders(ASD),in the hippocampus(DG and CA1–4)of adolescent rhesus monkeys(Macaca mulatta)in vivo via adeno-associated virus(AAV)-delivered Staphylococcus aureus Cas9 with small guide RNAs(sg RNAs)targeting MECP2.In comparison to monkeys injected with AAV-Sa Cas9 alone(n=4),numerous autistic-like behavioral abnormalities were identified in the AAV-Sa Cas9-sg MECP2-injected monkeys(n=7),including social interaction deficits,abnormal sleep patterns,insensitivity to aversive stimuli,abnormal hand motions,and defective social reward behaviors.Furthermore,some aspects of ASD and RTT,such as stereotypic behaviors,did not appear in the MECP2 gene-edited monkeys,suggesting that different brain areas likely contribute to distinct ASD symptoms.This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates,paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development. 展开更多
关键词 Autism spectrum disorders Nonhuman primate model Disease model Gene-editing
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Transgenic Nonhuman Primate Models for Human Diseases:Approaches and Contributing Factors 被引量:5
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作者 Yongchang Chen 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2012年第6期247-251,共5页
Nonhuman primates (NHPs) provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to ... Nonhuman primates (NHPs) provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to humans. Therefore, NHPs are appropriate models for the study of human diseases, such as neurodegenerative diseases including Parkinson's, Alzheimer's and Huntington's diseases, which occur as a result of genetic mutations. However, such diseases afflicting humans do not occur naturally in NHPs. So transgenic NHPs need to be established to understand the etiology of disease pathology and pathogenesis. Compared to rodent genetic models, the generation of transgenic NHPs for human diseases is inefficient, and only a transgenic monkey model for Huntington's disease has been reported. This review focuses on potential approaches and contributing factors for generating transgenic NHPs to study human diseases. 展开更多
关键词 Nonhuman primates Disease model TRANSGENESIS
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Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina 被引量:4
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作者 Shouzhen Li Yingzhou Hu +15 位作者 Yunqin Li Min Hu Wenchao Wang Yuqian Ma Yuan Cai Min Wei Yichuan Yao Yun Wang Kai Dong Yonghao Gu Huan Zhao Jin Bao Zilong Qiu Mei Zhanga Xintian Hu Tian Xue 《Science Bulletin》 SCIE EI CSCD 2021年第4期374-385,M0004,共13页
Retinitis pigmentosa(RP)is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the rodents.Therefore,creating nonhuman primate(NHP)models of RP... Retinitis pigmentosa(RP)is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the rodents.Therefore,creating nonhuman primate(NHP)models of RP is of critical importance to study its mechanism of pathogenesis and to evaluate potential therapeutic options in the future.Here we applied adeno-associated virus(AAV)-delivered CRISPR/SaCas9 technology to knockout the RHO gene in the retinae of the adult rhesus macaque(Macaca mulatta)to investigate the hypothesis whether non-germline mutation of the RHO gene is sufficient to recapitulate RP.Through a series of studies,we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein expression.More importantly,the mutant macaque retinae displayed clinical RP phenotypes,including photoreceptor degeneration,retinal thinning,abnormal rod subcellular structures,and reduced photoresponse.Therefore,we suggest somatic editing of the RHO gene is able to phenocopy RP,and the reduced time span in generating NHP mutant accelerates RP research and expands the utility of NHP model for human disease study. 展开更多
关键词 Nonhuman primate model Retinitis pigmentosa RHODOPSIN Disease model Gene editing SaCas9
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Technology advancing the study of animalcognition: using virtual reality to presentvirtually simulated environments to investigatenonhuman primate spatial cognition 被引量:1
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作者 Francine L. DOLINS Kenneth SCHWELLER Scott MILNE 《Current Zoology》 SCIE CAS CSCD 2017年第1期97-108,共12页
Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans (e.g., Woollett et al. 2009). The use of such interactive technologyhas increasingly becom... Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans (e.g., Woollett et al. 2009). The use of such interactive technologyhas increasingly become an essential part of modern life (e.g., autonomously driving vehicles, glo-bal positioning systems (GPS), and touchscreen computers; Chinn and Fairlie 2007; Brown 2011).While many nonhuman animals have their own forms of technology, such as chimpanzees whocreate and use tools, in captive animal environments the opportunity to actively participate withinteractive technology is not often made available. Exceptions can be found in some state-of-the-art zoos and laboratory facilities (e.g., Mallavarapu and Kuhar 2005). When interactive technologyis available, captive animals often selectively choose to engage with it. This enhances the animal'ssense of control over their immediate surroundings (e.g., Clay et al. 2011; Ackerman 2012). Suchself-efficacy may help to fulfill basic requirements in a species' daily activities using problem solv-ing that can involve foraging and other goal-oriented behaviors. It also assists in fulfilling thestrong underlying motivation for contrafreeloading and exploration expressed behaviorally bymany species in captivity (Young 1999). Moreover, being able to present nonhuman primates vir-tual reality environments under experimental conditions provides the opportunity to gain insightinto their navigational abilities and spatial cognition. It allows for insight into the generation andapplication of internal mental representations of landmarks and environments under multiple con-ditions (e.g., small- and large-scale space) and subsequent spatial behavior. This paper reviewsmethods using virtual reality developed to investigate the spatial cognitive abilities of nonhumanprimates, and great apes in particular, in comparison with that of humans of multiple age groups.We make recommendations about training, best practices, and also pitfalls to avoid. 展开更多
关键词 animal cognition apes bonobos chimpanzees nonhuman primates spatial cognition virtual reality.
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A functional paradigm for evaluating culture: An example with cetaceans 被引量:1
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作者 Alison Linda GREGGOR 《Current Zoology》 SCIE CAS CSCD 2012年第2期271-286,共16页
Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially trans... Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially transmitted, group specific behavior. Not surprisingly, evidence for culture has accrued in several taxonomic groups, including cetaceans. If culture is an ada- ptation, it is imperative we understand the factors that favor its formation. Understanding the evolutionary origin of culture will allow for a wider range of species to be studied, including those that are difficult to test in the laboratory. I propose a broad-based functional paradigm for evaluating nonhuman culture; based on the idea that while not all cultural behaviors may garner fitness benefits to the individual, the ecological and social environments in which cultural behaviors evolved must have favored the physical attributes and social learning capabilities that allow for cultural formation. Specifically this framework emphasizes the relationships between social learning, ecology, social systems, and biology in relation to culture. I illustrate the utility of the func- tional paradigm with evidence from the ceteacean group, while setting the stage for a stringent species by species analysis. By means of contextualizing culture, the Functional Paradigm can evaluate a species' potential to exhibit culture and can investigate potentially cultural behaviors 展开更多
关键词 Nonhuman culture Social learning Evolutionary fimction CETACEANS
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Assessing the nonhuman primate reservoir of Schistosoma mansoni in Africa:a systematic review 被引量:1
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作者 Lindsay Richards Berhanu Erko +2 位作者 Keerati Ponpetch Sadie J.Ryan Song Liang 《Infectious Diseases of Poverty》 SCIE 2019年第3期10-20,共11页
Background:Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates(NHPs)in Africa,coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas,h... Background:Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates(NHPs)in Africa,coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas,has led to concerns about the role of NHPs in the transmission of human schistosomiasis.We conducted a systematic review of the literature to describe the current scope of knowledge for Africa,for the NHP species implicated,their geographical distribution,infection rates with 5.mansoni,and to discuss the implications for public health and conservation.Main text:A systematic search of the literature was performed using PubMed,Web of Science,Google Scholar,the World Health Organization(WHO)library database,World Cat,and ScienceDirect without any language restriction.Studies examining 5.monsoni infeaion of any African NHP species were included.Study types,primate species,their geographical distribution,and parasite diagnostic techniques reported in the studies were qualitatively summarized.Data for species with sample sizes>10 were included in the meta-analysis.We assessed the reported infection rate,and used a random-effeas model to estimate the summary infeaion rates and 95%confidence intervals(C/s).We assessed heterogeneity among studies using the I2 statistics.Twenty-nine publications,from 1960 to 2018,were identified and included in the review.The studies examined a total of 2962 primates belonging to 22 species in 11 genera across ten countries(Cameroon,Eritrea,Ethiopia,Gabon,Kenya,Nigeria,Senegal,Tanzania,Uganda,and Zimbabwe),and 5.mansoni infeaions were found in nine species of five genera in all countries.When we excluded studies with sample sizes<10,data from 24 studies on 11 species of primates in three genera in ten countries remained in the meta-analysis.The overall pooled estimate of infection rate was 10%(95%Cl:6-16%)with high heterogeneity(I^2=9477%)across countries and species/genera.Among the three genera,Pan had the highest infection rate of 15%(95%CI:0-55%),followed by Popio at 11%(95%Cl:6-18%),and Cercopithecus at 5%(95%CI:0-14%).The association between NHP and human infections was positive,but not significant,due to low study sample matches and high variation.Conclusions:Our findings suggest that 5.mansoni infection rate is high in African NHPs,with substantial heterogeneities across spedes/genera and countries in Africa.Given the evidence for potential spillover and spillback of S.mansoni between African NHPs and humans,further research is urgently needed to understand ecology and mechanisms of transmission of the parasite between NHP and human hosts,in order to inform control strategies of this important neglected tropical disease. 展开更多
关键词 Schistosomo monsoni Nonhuman primate Infeaion TRANSMISSION Systematic review AFRICA
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