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• W2049063465 abstract "Site- and time-specific somatic gene transfer by using the avian sarcoma-leukosis retrovirus RCAS (replication-competent avian sarcoma-leukosis virus long terminal repeat with splice acceptor) has been shown to be a powerful tool to analyze gene function in vivo . RCAS retroviruses that express the avian subgroup A envelope transduce only mammalian cells genetically engineered to express the avian retroviral receptor, tumor virus A (TVA). Here, we generated a knockin mouse line termed LSL-R26 Tva-lacZ with concomitant conditional expression of TVA and lacZ by targeting the Rosa26 locus. A loxP-flanked transcriptional stop cassette was used for conditional activation of TVA and LacZ expression in a Cre-recombinase-dependent manner. To demonstrate the ability of this system for conditional somatic gene transfer in vivo , we directed TVA expression to the pancreas. Introduction of an RCAS vector with Bryan-RSV polymerase and subgroup A envelope [RCASBP(A)] carrying oncogenic Kras G12D induced focal ductal pancreatic lesions that recapitulate human pancreatic intraepithelial neoplasias that progress to pancreatic ductal adenocarcinomas. TVA-mediated infection of genetically engineered mice with endogenous expression of Kras G12D in pancreatic progenitor cells by using RCASBP(A) virus carrying a short hairpin RNA directed against murine TP53, resulted in dramatically enhanced progression to invasive adenocarcinomas. These results show that conditional expression of TVA enables spatiotemporal gene expression and knockdown in a small subset of somatic cells in vivo . Therefore, it closely models carcinogenesis in humans where tumors evolve from somatic gene mutations in developmentally normal cells. Combined with the growing number of Cre expression models, RCAS-TVA-based gene expression and knockdown systems open up promising perspectives for analysis of gene function in a time-controlled and tissue-specific fashion in vitro and in vivo ." @default.
• W2049063465 created "2016-06-24" @default.
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• W2049063465 date "2008-07-22" @default.
• W2049063465 modified "2023-09-26" @default.
• W2049063465 title "A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown <i>in vivo</i> by using avian retroviral vectors" @default.
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• W2049063465 doi "https://doi.org/10.1073/pnas.0800487105" @default.
• W2049063465 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2481330" @default.
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