Mechanism of alopecia in the new hairless mutant Hos: HR-1 mouse

ABSTRACT: The Hos: HR-1 mouse strain (HR-1) is an autosomal resessive mutant strain which is widely used in pharmacological and dermatological studies in Japan. Although HR-1 mice have been believed to be Hr gene mutants based on their distinctive alopecia phenotype, there are no reports on either the genetic nature of the Hr gene or mechanism of alopecia. The present study clarified that the HR-1 mice carry a C to T transition in the Hr gene, which causes a proline to serin amino acid change in the functional domain of translated HR protein. It is well known that HR plays an important role in hair follicle regression, and loss of HR function triggers distinctive alopecia with the presence of premature apoptosis in the regressing hair follicle. However, the detailed function of HR protein is still uncertain. To clarify the mechanism by which HR dysfunction causes hair loss, here we performed microarray analysis on the mRNA samples obtained from the regressing hair follicles of the homozygous (HrHos / HrHos) and heterozygous (+/HrHos, control) Hr mutant mice using laser capture microdissection. Our results showed increased expression of apoptosis-related and cell-cycle-repressive genes and decreased expression of cell-cycle-promoting genes, suggesting inhibition of the cell cycle at G0/G1. These findings strongly suggest that the loss of HR function leads to high expression of cell cycle inhibitors, resulting in the hair loss with premature apoptosis in the hair matrix. Keywords: genetic analysis

ORGANISM(S): Mus musculus

PROVIDER: GSE6866 | GEO | 2008/07/11

SECONDARY ACCESSION(S): PRJNA99117

REPOSITORIES: GEO