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A comparative analysis of selenoproteins and global gene expression in liver selenocysteine tRNA knockout mice and its rescued variants
Author(s) -
Sengupta Aniruddha,
Weaver James A,
Novoselov Sergey V,
Fomenko Dmitri E,
Carlson Bradley A,
Gladyshev Vadim N,
Hatfield Dolph L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a427-d
Subject(s) - selenocysteine , gene , biology , knockout mouse , gene knockout , gene expression , selenoprotein , mutant , transfer rna , detoxification (alternative medicine) , dna microarray , microbiology and biotechnology , genetics , biochemistry , rna , enzyme , glutathione , cysteine , medicine , glutathione peroxidase , alternative medicine , pathology
Selenium (Se) is an essential micronutrient for mammals, being incorporated into selenoproteins (SPs) as the 21st amino acid, selenocysteine (Sec). Rodents and humans encode 24 and 25 SP genes, respectively. SPs are tissue specific, performing biologically diverse functions. Sec expression is dependent on Sec tRNA, thus, manipulating the expression of Sec tRNA can alter SP expression. Targeted removal of the Sec tRNA gene ( trsp ) in liver demonstrated the significance of SPs in liver function (Carlson et al., J. Biol. Chem. , 2004, 279 :). The SP population was replaced in these mice with mutant variants of trsp (A34 and G37) and microarrays were used for comparative analysis of gene expression in liver of knockout and rescued mice. The SPs in these mice were further assessed through real‐time PCR. Studies revealed a loss of expression of most SPs in the knockout mice with an enhanced expression of some detoxification genes. However, in the replacement mice, most SPs were expressed similar to the wild type with a corresponding decrease in the expression of detoxification genes as compared to the knockout. Taken together, the data suggest a relationship between SPs and detoxification processes, wherein some specific SPs may be compensated for by the upregulation of genes involved in detoxification in liver of the knockout mouse. This research was supported by the Intramural Research Program of the NIH, NCI, CCR, and by NIH GM061603.