P3.31 The gene for hair-loss disorder in HWY (Hairless Wistar Yagi) rat maps to chromosome 15 near hairless gene

Ishii Y., Kyuwa S., and Yoshikawa Y.

Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, JAPAN

Objectives: HWY (Hairless Wistar Yagi) rat was found in a colony of rats of Wistar strain in 1982 and has been maintained as an inbred strain. In this mutant, short pelage is sparsely distributed at weaning but, by their maturity, they exhibit almost complete hairlessness. This hairless phenotype of HWY strain is due to an autosomal semidominant gene, and F₁ hybrids between HWY and normal Wistar strain have twisted and sparse pelage throughout their lifetime. In this study, we carried out linkage analysis using F₂ intercross between HWY and BN strains, to identify the causative gene, provisionally named HWY.

Results and Conclusions: The result indicated that the HWY gene is located on rat chromosome (Chr) 15, and the locus order was D15Wox9/Clu - (0.520 cM) - D15rat15 - (0.173 cM) - HWY - (0.087 cM) - Rb1 - (0.173 cM) - D15Got59. The HWY gene showed no recombination with 12 polymorphic markers investigated including Stc1 and Sftpc in 1154 meioses. A BLAST search on these polymorphic markers suggested that the critical region of the HWY gene is conserved among rat Chr15, mouse Chr14 and human Chr8p. The hairless (hr), known as the causative gene for both hairless mice and Alopecia Universaris in human, is localized in this region. However, the sequencing of the hr cDNA from HWY rat revealed only one silent mutation, and the expression level of hr mRNA in the mutant skin was almost equivalent to that of control rat skin. These results provide the possibility that HWY is a novel hair-growth regulatory gene distinct from hr gene.