| First Author | Tullis K | Year | 1998 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:50058 |
| Mgi Id | MGI:1303248 | Citation | Tullis K, et al. (1998) Mapping of the mouse Constitutive Androstane Receptor gene (Care2) to Chromosome 1. MGI Direct Data Submission |
| abstractText | CAR is a liver-specific member of the nuclear hormone receptor superfamily that heterodimerizes with 9-cis-retinoic acid receptors (RXRs) to activate transcription from retinoic acid response elements (RAREs) (1. Forman BM, Tzameli I, Choi H-S, Chen J, Simha D, Seol W, Evans RM and Moore DD (1998) Nature 395:812-5). First cloned as a cDNA from human liver, MB67, mCAR was subsequently characterized from mouse, where, like other orphan receptors, a ligand was not evident and activation appeared to be constitutive (CAR, Constitutive Activator in the Retinoid pathway). Recently, androgen metabolites have been identified as specific ligands for CAR, leading to dubbing the gene Care2, for Constitutive Androstane Receptor. In contrast to other nuclear receptors, in the presence of its ligands CAR is not transcriptionally. That CAR is a liver-specific factor whose activity is controlled by androgen metabolites made it an appealing candidate gene product for the Rsl (regulator of sex-limitation) gene. Rsl is a trans-acting regulator of mouse sex-limited protein (Slp), which is normally expressed only in adfult male mice and predominantly in liver. In mice homozygous for rsl alleles, females as well as males initiate Slp expression at puberty, and males express higher than normal Slp levels. This and other data suggest that Rsl acts to repress transcription of the Slp gene in both sexes; repression is overcome in males by hormonal induction at puberty. Mutations in Rsl relieve repression and allow Slp expression in females as well as males, regardless of induction. Rsl could encode the repressor itself or a protein that regulates the repressor. Because CAR is a liver-specific transcription factor that is negatively regulated by products of androgen metabolism, we thought it a compelling candidate for Rsl, which has been mapped to a narrow interval of Chromosome 13 (2. Jiang PP, Frederick K, Hansen TH, and Miller RD (1996) Proc Natl Acad Sci U S A 93:913-7). Using primers designed to flank a CA/GT repeat int he 5' UTR, Care showed no linkage to Rsl and instead maps to Chromosome 1. Thus, CAR is not the product of the Rsl locus. However, it may be a downstream target of Rsl that regulates sexually dimorphic Slp gene expression. |
