Spermatogonial stem cells(SSCs)transmit genetic information to the next progeny in males.Thus,SSCs are a potential target for germ I i ne modifications to gen erate tran sgenic an imals.In this study,we report a techn...Spermatogonial stem cells(SSCs)transmit genetic information to the next progeny in males.Thus,SSCs are a potential target for germ I i ne modifications to gen erate tran sgenic an imals.In this study,we report a technique for the gen erati on of tran sgenic rats by in vivo manipulation of SSCs with a high success rate.SSCs in juvenile rats were transduced in vivo with high titers of lentivirus harbori ng enhan ced green fluoresce nt protei n and mated with wild-type females to create foun der rats.These founder rats expressed the transgene and passed on the transgene with an overall success rate of 50.0%.Subsequent generations of progeny from the founder rats both expressed and passed on the transgene.Thus,direct modification of SSCs in juvenile rats is an effective means of generating transgenic rats through the male germline.This technology could be adapted to larger animals,in which existing methods for gene modificatio n are in adequate or in applicable,resulti ng in the gen eration of tran sge nic an imals in a variety of species.展开更多
Obesity has become an important public problem that endangers human conditions and urgently needs to be solved. However,most weight-loss drugs on the market have little effect and are accompanied by adverse effects su...Obesity has become an important public problem that endangers human conditions and urgently needs to be solved. However,most weight-loss drugs on the market have little effect and are accompanied by adverse effects such as strokes and heart attacks.Here, we construct an adipocyte-targeting polypeptide-based gene carrier consisting of an adipocyte-targeting peptide and ptoluylsulfonyl arginine-modified polylysine(ATS-PLL-RT), which can specifically bind to the prohibitin of mature adipocytes.We further construct a short hairpin RNA(shRNA) to simultaneously silence fatty acid binding proteins 4 and 5(shFABP4/5).FABPs are molecular chaperones for fatty acid metabolism and storage in cells. Moreover, we introduce metformin for combined therapy. First, the metformin combination can effectively improve the efficiency of gene transfection. In addition, metformin itself has an alleviating effect on diet-induced obesity and relevant metabolic diseases. The combination treatment of obese mice with ATS-PLL-RT/shFABP4/5 and metformin achieves body weight reduction and metabolic recovery. This study provides a potentially effective strategy for the clinical treatment of obesity as well as mitigating obesity-induced metabolic syndromes.展开更多
文摘Spermatogonial stem cells(SSCs)transmit genetic information to the next progeny in males.Thus,SSCs are a potential target for germ I i ne modifications to gen erate tran sgenic an imals.In this study,we report a technique for the gen erati on of tran sgenic rats by in vivo manipulation of SSCs with a high success rate.SSCs in juvenile rats were transduced in vivo with high titers of lentivirus harbori ng enhan ced green fluoresce nt protei n and mated with wild-type females to create foun der rats.These founder rats expressed the transgene and passed on the transgene with an overall success rate of 50.0%.Subsequent generations of progeny from the founder rats both expressed and passed on the transgene.Thus,direct modification of SSCs in juvenile rats is an effective means of generating transgenic rats through the male germline.This technology could be adapted to larger animals,in which existing methods for gene modificatio n are in adequate or in applicable,resulti ng in the gen eration of tran sge nic an imals in a variety of species.
基金supported by the National Key Research and Development Program of China(2021YFB3800900)the National Natural Science Foundation of China(51925305,51873208,51973217,51520105004,51803210)Jilin Province Science and Technology Development Program(20180414027GH,20200201075JC,20210509005RQ)。
文摘Obesity has become an important public problem that endangers human conditions and urgently needs to be solved. However,most weight-loss drugs on the market have little effect and are accompanied by adverse effects such as strokes and heart attacks.Here, we construct an adipocyte-targeting polypeptide-based gene carrier consisting of an adipocyte-targeting peptide and ptoluylsulfonyl arginine-modified polylysine(ATS-PLL-RT), which can specifically bind to the prohibitin of mature adipocytes.We further construct a short hairpin RNA(shRNA) to simultaneously silence fatty acid binding proteins 4 and 5(shFABP4/5).FABPs are molecular chaperones for fatty acid metabolism and storage in cells. Moreover, we introduce metformin for combined therapy. First, the metformin combination can effectively improve the efficiency of gene transfection. In addition, metformin itself has an alleviating effect on diet-induced obesity and relevant metabolic diseases. The combination treatment of obese mice with ATS-PLL-RT/shFABP4/5 and metformin achieves body weight reduction and metabolic recovery. This study provides a potentially effective strategy for the clinical treatment of obesity as well as mitigating obesity-induced metabolic syndromes.
