Selective Removal of the Selenocysteine tRNA[Ser]Sec Gene (Trsp) in Mouse Mammary Epithelium

• DOI: 10.1128/mcb.23.5.1477-1488.2003
• Publication Date: 2003-02-14T20:05:17Z
• Authors: Easwari Kumaraswamy; Bradley A. Carlson; Fanta Morgan; Keiko Miyoshi; Gertraud W. Robinson; Dan Su; Shulin Wang; Eileen Southon; Lino Tessarollo; Byeong Jae Lee; Vadim N. Gladyshev; Lothar Hennighausen; Dolph L. Hatfield
• Keywords: Selenocysteine

Mice homozygous for an allele encoding the selenocysteine (Sec) tRNA [Ser]Sec gene (Trsp) flanked by loxP sites were generated. Cre recombinase-dependent removal of Trsp in these mice was lethal to embryos. To investigate role mouse mammary epithelium, we deleted this using transgenic carrying recombinase under control tumor virus (MMTV) long terminal repeat or whey acidic protein promoter. While both promoters target expression MMTV-Cre is also expressed spleen and skin. Sec amounts reduced more than 70% tissue with either transgene, while skin spleen, levels only MMTV-Cre. The selenoprotein population selectively affected breast but not tissue, kidney. Moreover, within tissues, specific selenoproteins regulated differently often a contrasting manner, Sep15 glutathione peroxidases GPx1 GPx4 being substantially reduced. Expression suppressor genes BRCA1 p53 altered manner mice, suggesting greater susceptibility cancer and/or increased cell apoptosis. Thus, conditional knockout allows tissue-specific manipulation expression, that approach will provide useful tool studying health.