International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 21 - POSITIONAL CLONING OF THE CAUSATIVE GENE FOR TWO MOUSE SKIN MUTATIONS, RIM3 AND REDEN

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

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

A mouse skin mutant, Recombinant-induced mutation 3 (Rim3), exhibits dominant phenotype of hyperkeratosis and hair follicle degeneration, which arose spontaneously in an intra-MHC recombinant strain B10.BR(228) in 1989. Rim3 was mapped to proximity of another mutant, Rex denuded (Reden), in chromosome 11. Both mutants showed resembling skin phenotype, and we proposed that Rim3 and Reden are allelic (Sato et al., 1998). Physical mapping in our previous study had narrow downed the Rim3 critical region to a ~200kb region covered by 2 BAC clones. We isolated a candidate gene, which is expressed both in skin and gastric duct, and named Gasdermin (Gsdm). However, no alteration was found in Gsdm of Rim3 and Reden mutants.

In this study, we searched new candidate genes for genome database, and found two genes that are paralogues of Gsdm. We named this novel gene cluster GasdeminA (GsdmA), and the three paralogus genes, GsdmA1 (former Gsdm), -A2 and -A3. The GsdmA cluster genes have no known motif except for leucine-zipper. Sequence analysis revealed a point mutation and 6 bases insertion in the GsdmA3 gene of Rim3 and Reden, respectively. RT-PCR and in situ hybridization analysis showed that GsdmA3 is expressed in epidermis and/or hair follicles from postnatal stage. BrdU labeling and immunohistochemical analysis with epidermal cells-specific markers demonstrated hyperproliferation and misdifferentiation of the upper follicular epidermis in Rim3. All data suggest that GsdmA3 controls proliferation and differentiation of epidermal keratinocytes.


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