International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 53 - ANALYSIS OF CANDIDATE GENE FOR A MOUSE MUTANT, RECOMBINATION-INDUCED MUTATION 3 (RIM3), WITH IMPAIRED EPIDERMAL MORPHOGENESIS

S Tanaka
Grad. Univ. Advanced Studies, Natl. Inst. Genet.

1) Tanaka S, 2) Aoki A, 3) Sato H, 4) Saeki N, 1) Tamura M, 5) Shiroishi T
1) Grad. Univ. Advanced Studies, Natl. Inst. Genet. 2) Natl. Inst. Genet., Juntendo Univ. 3)Tohoku Univ. 4) Natl. Cancer Cent. Res. Inst. 5) Grad. Univ. Advanced Studies, Natl. Inst. Genet.

Epidermis and hair follicles are generated from epidermal stem cells that have an ability of self-renewal. The epidermal stem cells reside in both basal layer and bulge of hair follicles. While the stem cells in basal layer differentiate into epidermal keratinocytes, those in bulge give rise not only to hair follicles but also to epidermis. However, the molecular mechanism by which epidermal stem cells differentiate is poorly understood. Recombination-induced mutation 3 (Rim3) is a mouse mutation that exhibits hyperkeratosis and hair follicle degeneration. To characterize the epidermis of Rim3, we analyzed proliferation of the epidermal cells by BrdU labeling, and carried out immunohistochemical analysis with epidermal cells specific marker. We found hyperproliferation of the upper follicular epidermis, and it appeared that cells in the hair follicles differentiate into epidermal keratinocytes. These data suggest that the bulge stem cells differentiate epidermal keratinocytes, and the progeny cell migrates upward to the follicular epidermis rather than to the lower hair follicles, which results in hair follicle degeneration in Rim3. In order to search the responsible gene for Rim3, Rim3 was mapped to the mouse chromosome 11 based on a total of 2,212 backcross progeny. Physical mapping narrowed down the Rim3 critical region to about a 200 kb region that is covered by 2 BAC clones. We performed cDNA selection using the mouse skin cDNA library and the BAC clones, and isolated several cDNA clones as candidates for Rim3 causative gene. The genome DNA of Rim3 was sequenced to search mutation.


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