The 'Bald Mill Hill' Mutation in the Mouse Is Associated with an Abnormal, Mislocalized HR BMH Protein

The study investigated the "Bald Mill Hill" (bmh) mutation in mice, which resulted in an abnormal Hairless (HR) protein due to a 296bp deletion. This mutation produced a larger HR protein with an additional 117 amino acids, affecting its function and localization. The mutant HR protein could still bind to the vitamin D receptor (VDR) but failed to repress VDR-mediated transactivation, a function normally performed by the wild-type HR protein. The mislocalization of the mutant HR protein to the cytoplasm, rather than the nucleus, likely contributed to its impaired function in hair follicle development, leading to the hairless phenotype observed in mutant mice. The study highlighted the importance of HR protein localization for proper hair follicle morphogenesis and cycling.