The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome...The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome manipulations in rabbit has been stalled for decades,severely limiting its applications in biomedical research.Novel genome editing technologies,especially CRISPR/Cas9,have remarkably enhanced precise genome manipulation in rabbits,and shown their superiority and promise for generating rabbit models of human genetic diseases.In this review,we summarize the brief history of transgenic rabbit technology and the development of novel genome editing technologies in rabbits.展开更多
The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interestingcandidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic...The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interestingcandidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cellnuclear transfer (SCNT) to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs expressapproximately 15–25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was alsomarkedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs withinfluenza A virus and classical swine fever virus (CFSV). Indirect immunofluorescence assay (IFA) revealed a profounddecrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-foldreduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found thatthe Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These resultsdemonstrate that the Mx1 transgene can protect against viral infection in cells of transgenic pigs and indicate thatthe Mx1 transgene can be harnessed to develop disease-resistant pigs.展开更多
Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not t...Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not transferable to human.To address these issues,we developed SysFinder(http://lifecenter.sgst.cn/SysFinder),a platform for scientists to find appropriate animal models for translational research.SysFinder offers a "topic-centered" approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal models.Scientific topic can be a certain disease,drug,gene function or biological pathway.SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics.Meanwhile,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models.Furthermore,SysFinder provides a userfriendly platform for determination of short guide RNAs(sgRNAs) and homology arms to design a new animal model.Case studies illustrate the ability of SysFinder in helping experimental scientists.SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.展开更多
文摘The rabbit has been recognized as a valuable model in various biomedical and biological research fields because of its intermediate size and phylogenetic proximity to primates.However,the technology for precise genome manipulations in rabbit has been stalled for decades,severely limiting its applications in biomedical research.Novel genome editing technologies,especially CRISPR/Cas9,have remarkably enhanced precise genome manipulation in rabbits,and shown their superiority and promise for generating rabbit models of human genetic diseases.In this review,we summarize the brief history of transgenic rabbit technology and the development of novel genome editing technologies in rabbits.
基金This work was supported by grants from National Basic Research Program of China(973 program)(2011CB944203)ZNGI-2011-010 from the Guangzhou Municipality and the Chinese Academy and Sciences to L.L.
文摘The myxovirus resistance gene (Mx1) has a broad spectrum of antiviral activities. It is therefore an interestingcandidate gene to improve disease resistance in farm animals. In this study, we report the use of somatic cellnuclear transfer (SCNT) to produce transgenic pigs over-expressing the Mx1 gene. These transgenic pigs expressapproximately 15–25 times more Mx1 mRNA than non-transgenic pigs, and the protein level of Mx1 was alsomarkedly enhanced. We challenged fibroblast cells isolated from the ear skin of transgenic and control pigs withinfluenza A virus and classical swine fever virus (CFSV). Indirect immunofluorescence assay (IFA) revealed a profounddecrease of influenza A proliferation in Mx1 transgenic cells. Growth kinetics showed an approximately 10-foldreduction of viral copies in the transgenic cells compared to non-transgenic controls. Additionally, we found thatthe Mx1 transgenic cells were more resistant to CSFV infection in comparison to non-transgenic cells. These resultsdemonstrate that the Mx1 transgene can protect against viral infection in cells of transgenic pigs and indicate thatthe Mx1 transgene can be harnessed to develop disease-resistant pigs.
基金supported by the National High Technology Research and Development Program of China(No.2015AA020104)the National Key Research and Development Program on Precision Medicine(No.2016YFC0901700)+6 种基金the National Basic Research Program of China(Nos.2011CB910204,2011CB510102,and 2010CB529200)the National Key Technology Support Program (No.2013BA1101B09)the National Key Scientific Instrument and Equipment Development Project(No.2012YQ03026108)the National Grand Program on Key Infectious Diseases(No. 2015ZX10004801)the Medical-Engineering Cross Project of Shanghai Jiao Tong University(No.YG2016MS33)the Youth Innovation Promotion Association CASthe National Institutes of Health grants(Nos.R01HL117491 and R01HL129778 to Y.E.C)
文摘Animal models are increasingly gaining values by cross-comparisons of response or resistance to clinical agents used for patients.However,many disease mechanisms and drug effects generated from animal models are not transferable to human.To address these issues,we developed SysFinder(http://lifecenter.sgst.cn/SysFinder),a platform for scientists to find appropriate animal models for translational research.SysFinder offers a "topic-centered" approach for systematic comparisons of human genes,whose functions are involved in a specific scientific topic,to the corresponding homologous genes of animal models.Scientific topic can be a certain disease,drug,gene function or biological pathway.SysFinder calculates multi-level similarity indexes to evaluate the similarities between human and animal models in specified scientific topics.Meanwhile,SysFinder offers species-specific information to investigate the differences in molecular mechanisms between humans and animal models.Furthermore,SysFinder provides a userfriendly platform for determination of short guide RNAs(sgRNAs) and homology arms to design a new animal model.Case studies illustrate the ability of SysFinder in helping experimental scientists.SysFinder is a useful platform for experimental scientists to carry out their research in the human molecular mechanisms.