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Functional Analysis of C-CAM1 Tumor Suppressor Gene by Targeted Gene Deletion

机译:靶向基因缺失对C-Cam1肿瘤抑制基因的功能分析

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CEACAM1 is a cell adhesion molecule. Alternative splicing of the Ceacam1 gene generated two isoforms of CEACAM1, i.e. CEACAM1-L (long form) and CEACAM1-S (short form). We have shown that CEACAM1-L plays critical roles in prostate cancer progression. We propose to determine the function of CEACAM1 in prostate development, prostate homeostasis and prostate tumorigenesis by using gene targeting technologies. Specifically, we plan to generate mice with a targeted deletion of the CEACAM1 cytoplasmic domain. We have constructed a Ceacam1 targeting vector in which exons 7-9 of Ceacam1 gene was flanked by loxP sites for the generation of conditional knockout of the Ceacam1 gene. Embryonic stem cell clones containing the recombinant gene allele were established and injected into blastocysts for germ line transmission of the targeting construct; We have succeeded in producing mice harboring the conditional Ceacam1 knockout allele. In this extended period, we generated mice with homozygote conditional Ceacam1 allele and characterized the expression of CEACAM1 protein. In addition, we have crossed the homozygote conditional Ceacam1 mice with transgenic mice containing probasin-driven cre to generate mice with prostate-specific deletion of Ceacam1 gene. Initial analysis of 3 month old mouse prostates showed that deletion of Ceacam1-L in the mouse prostates led to epithelial hyperplasia.

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