conditional wwox deletion in mouse mammary gland by means of two cre recombinase approaches条件wwox基因缺失小鼠乳腺通过两种cre重组酶的方法.pdfVIP

Conditional Wwox Deletion in Mouse Mammary Gland by Means of Two Cre Recombinase Approaches 1 1 1 1 1 2 Brent W. Ferguson , Xinsheng Gao , Hyunsuk Kil , Jaeho Lee , Fernando Benavides , Martin C. Abba , C. Marcelo Aldaz1* 1 Department of Molecular Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas, United States of America, 2 CINIBA, Facultad de Medicina, Universidad Nacional de La Plata, La Plata, Argentina Abstract Loss of WWOX expression has been reported in many different cancers including breast cancer. Elucidating the function of this gene in adult tissues has not been possible with full Wwox knockout models. Here we characterize the first conditional models of Wwox ablation in mouse mammary epithelium utilizing two transgenic lines expressing Cre recombinase, keratin 5-Cre (BK5-Cre) and MMTV-Cre. In the BK5-Cre model we observed very efficient Wwox ablation in KO mammary glands. However, BK5-Cre Wwox KO animals die prematurely for unknown reasons. In the MMTV-Cre model we observed significant ablation of Wwox in mammary epithelium with no effect on survival. In both of these models we found that Wwox deletion resulted in impaired mammary branching morphogenesis. We demonstrate that loss of Wwox is not carcinogenic in our KO models. Furthermore, no evidence of increase proliferation or development of premalignant lesions was observed. In none of the models did loss of a single Wwox allele (i.e. haploinsufficiency) have any observable phenotypic effect in mammary gland. To better understand the function of Wwox in the mammary gland, transcriptome profiling was performed. We observed that Wwox ablation results in the deregulation of genes inv