A Novel Missense Mutation in the Mouse Hairless Gene Causes Irreversible Hair Loss: Genetic and Molecular Analyses of Hrm1Enu

The study identified a novel missense mutation in the mouse hairless gene (Hr) caused by ENU mutagenesis, leading to irreversible hair loss and skin wrinkling in homozygous mutant mice. This mutation involved a G-to-T transition in exon 15, resulting in a glycine-to-tryptophan substitution at amino acid 960, which affected the HR protein's function as a transcriptional corepressor. The mutation was inherited as an autosomal recessive trait, with 11 out of 52 mice displaying the hairless phenotype. It was linked to increased expression of genes like keratin complex 1 and vitamin D receptor, suggesting interference with HR's repression activity. The study provided insights into the genetic basis of hair loss and the role of HR in hair follicle development, offering a new animal model, Hrm1Enu, for studying human alopecia phenotypes.