| First Author | Compton JG | Year | 1988 |
| Journal | Mouse News Lett | Volume | 80 |
| Pages | 165-6 | Mgi Jnum | J:14275 |
| Mgi Id | MGI:62446 | Citation | Compton JG, et al. (1988) Keratin genes. Proximity to mutant loci on Chr 11 and Chr 15 that affect the epidermis, and linkage to homeobox homolog genes. Mouse News Lett 80:165-6 |
| abstractText | Full text of MNL contribution: Research News. 1. New mutants and linkages. c. Keratin Genes. Proximity to mutant loci on Chr 11 and Chr 15 that affect the epidermis, and linkage to homeobox homolog genes. We are investigating mouse keratin gene organization. We report initial results for K10 (type I, 59KDa), Kl (type II, 67KDa), and K6 (type II, 59.5KDa) by RFLP mapping. The keratin family of intermediate filament proteins (>30 genes) are divided into type I and type II subclasses, subsets of which are expressed in pairs in all epithelial tissues. For example, K10 and Kl are expressed upon differentiation of basal cells in cornifying epithelia such as the epidermis. K6 and K16 are coexpressed in hyperproliferating epithelial cells (e.g. during wound healing). Are such differentiation-specific keratin genes closely linked? Are coexpressed type I and type II genes intermingled, or rather are they clustered separately? Are keratin genes associated with mutant mouse loci? From our studies: 1) K10 has been found tightly linked to Re on Chr 11 using progeny from two backcrosses, (C57BL/6J-TrJ Re x M. spretus) Fl x C57BL/6J and (C57BL/6J-TrJ Re x SF/CamEi)Fl x C57BL/6J. A separation of <1.7 cM (95% U.C.L.) is calculated (0 crossovers/196). 2) Disparate SDPs were found in the BXH RI strains between K10 and Kl, suggesting no linkage between this pair of coexpressed type I and II genes (7 mismatches/12). 3) By contrast, only 1 mismatch was found between the SDPs for Kl and K6. These SDPs are identical to those of Int-1 and Gdc-1, respectively, suggesting linkage on Chr 15. Initial results from a backcross segregating for Gpt-1 and Gdc-1, (C57BL/6J x CAST/Ei)Fl x C53BL/6J, support this assignment. 4 ) Analysis of Hox-2 segregation in the TrJ Re x M. spretus backcross has yielded one crossover with Re(l/101), placing Hox-2 </= 1cM (95%) from Re. The presence of K10 close to loci that cause abnormal epidermal phenotypes (Re, Bsk, Den) expands the cluster of genes on the distal end of Chr 11 involved in epidermal tissue function. Moreover, our data, and that of others (Roderick, Taylor and Ruddle, pers. comm.), indicate that the homeobox homolog genes (Hox-2) also map at Re on Chr 11. We speculate that a homologous group of genes may exist on Chr 15, consisting of a cluster of skin-affecting loci (Ve, Sha, Ca, N), the Hox-3 locus (Awgulewitsch et al., 1986 Nature 320:328), and type II keratin genes (Kl and K6, at least). The probable derivation of type I and II keratin genes, and of Hox-2 and Hox-3 through duplicaton presents the possibility that the chromosomal segment encompassing K10 and Hox-2 may have been duplicated in a single event. Mapping studies to assess this interesting possibility are in progress. Finally, extrapolating from the syntenic mapping of Hox-2, Erba, and Glk on human Chr 17, and of Gdc-1, Hox-3 and Int-1 on human Chr 12, we suggest that the human keratin genes Kl0, and K1-K6 are located in human chromosomal regions 17ql11-17q22, and 12q12-12ql5, respectively. (Compton, S. Phillips and Nadeau) |
