Analysis of Hairless Gene Regulation and Identification of Affected Signaling Pathways in 'Bald Mill Hill' Mutants

The study focused on the Hairless (Hr) gene, which is crucial for hair follicle integrity and cycling in mammals. In the absence of functional Hairless protein, hair follicles undergo premature apoptosis, leading to irreversible hair loss. The research identified a 1.1 kb cis-control element (RE1) and a novel regulatory motif (UE60) that interact with thyroid and vitamin D receptors, suggesting a complex molecular network involved in hair follicle formation. The study used the "bald Mill Hill" mutant mice to explore vitamin D signaling, revealing that the mutant HR protein, although abnormally localized in the cytoplasm, interacts with the vitamin D receptor but fails to repress its activity. The HR protein's association with HDAC6 and its localization in endosomes and lysosomes suggest that endosomal processing and proteasome pathways might influence the hairless phenotype in these mutants.