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Publication : Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos.

First Author  Beronja S Year  2010
Journal  Nat Med Volume  16
Issue  7 Pages  821-7
PubMed ID  20526348 Mgi Jnum  J:160810
Mgi Id  MGI:4455214 Doi  10.1038/nm.2167
Citation  Beronja S, et al. (2010) Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos. Nat Med 16(7):821-7
abstractText  Using ultrasound-guided in utero infections of fluorescently traceable lentiviruses carrying RNAi or Cre recombinase into mouse embryos, we have demonstrated noninvasive, highly efficient selective transduction of surface epithelium, in which progenitors stably incorporate and propagate the desired genetic alterations. We achieved epidermal-specific infection using small generic promoters of existing lentiviral short hairpin RNA libraries, thus enabling rapid assessment of gene function as well as complex genetic interactions in skin morphogenesis and disease in vivo. We adapted this technology to devise a new quantitative method for ascertaining whether a gene confers a growth advantage or disadvantage in skin tumorigenesis. Using alpha1-catenin as a model, we uncover new insights into its role as a widely expressed tumor suppressor and reveal physiological interactions between Ctnna1 and the Hras1-Mapk3 and Trp53 gene pathways in regulating skin cell proliferation and apoptosis. Our study illustrates the strategy and its broad applicability for investigations of tissue morphogenesis, lineage specification and cancers.
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