a mouse strain where basal connective tissue growth factor gene expression can be switched from low to high鼠标应变,基底结缔组织生长因子基因表达可以切换从低到高.pdfVIP

A Mouse Strain Where Basal Connective Tissue Growth Factor Gene Expression Can Be Switched from Low to High 1,2 2 2 3,4 1,2 Heather E. Doherty , Hyung-Suk Kim , Sylvia Hiller , Kathleen K. Sulik , Nobuyo Maeda * 1 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 4 Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America Abstract Connective tissue growth factor (CTGF) is a signaling molecule that primarily functions in extracellular matrix maintenance and repair. Increased Ctgf expression is associated with fibrosis in chronic organ injury. Studying the role of CTGF in fibrotic disease in vivo, however, has been hampered by perinatal lethality of the Ctgf null mice as well as the limited scope of previous mouse models of Ctgf overproduction. Here, we devised a new approach and engineered a single mutant mouse strain where the endogenous Ctgf-39 untranslated region (39UTR) was replaced with a cassette containing two 39UTR sequences arranged in tandem. The modified Ctgf allele uses a 39UTR from the mouse FBJ osteosarcoma oncogene (c-Fos) and produces an unstable mRNA, resulting in 60% of normal Ctgf expression (Lo allele). Upon Cre-expression, excision of the c-Fos-39UTR creates a transcript ut