The Near-Naked Hairless (HrN) Mutation Disrupts Hair Formation but Is Not Due to a Mutation in the Hairless Coding Region

Near-naked hairless (HrN) is a semi-dominant, spontaneous mutation that was suggested by allelism testing to be allelic with mouse Hairless (Hr). HrN mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, rather than as an inability to regrow hair after the first catagen and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in HrN/HrN mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. HrN/HrN mice exhibit dystrophic hairs that are unable to emerge consistently from the hair follicle, whereas HrN/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in HrN/HrN mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr-coding region, intron–exon boundaries, 5′- and 3′-untranslated region, and immediate upstream region did not reveal the underlying mutation. Therefore, HrN does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.