The G60S Connexin43 Mutant Regulates Hair Growth and Hair Fiber Morphology in a Mouse Model of Human Oculodentodigital Dysplasia

Abstract

Patients expressing mutations in the gene encoding the gap junction protein Cx43 suffer from a disease called oculodentodigital dysplasia (ODDD). Patients with ODDD are often reported to develop hair that is dry, dull, sparse, and slow growing. To evaluate the linkage between Cx43 and hair growth, structure, and follicle density we employed a mouse model of ODDD that harbors a Cx43 G60S point mutant. Regionally sparse and overall dull hair were observed in mutant mice compared with their wild-type (WT) littermates. However, histological analysis of overall hair follicle density in mutant and WT mice did not reveal any significant differences. After epilation, mutant mouse hair grew back slower, and hair growth was asynchronous. In addition, ultrastructural scanning electron microscopic imaging of hair fibers taken from mutant mice and two patients harboring the G143S mutation revealed severe cuticle weathering. Nodule formation was also observed in the proximal region of hair fibers taken from mutant mice. These results suggest that the G60S mutant mouse model mimics the hair phenotype found in at least some ODDD patients and suggests an important role for Cx43 in hair regeneration, growth, and cuticle formation.