The molecular basis of congenital atrichia in humans and mice: Mutations in the hairless gene

Congenital atrichia is a form of total alopecia inherited in an autosomal r ecessive pattern. In individuals affected with this form of hair loss, hair s are typically absent from the scalp, and patients are nearly completely d evoid of eyebrows, eyelashes, axillary and pubic hair, following shedding o f the natural hair shortly after birth. We have recently linked this disord er to the chromosomal region 8p12, and cloned the human hairless gene, whic h resides within this interval. We have identified several mutations in the hairless gene in atrichia families from around the world. In hairless mice , the hair matrix cells appear to undergo a premature and massive apoptosis , together with a concomitant decline in Bcl-2 expression, a loss of NCAM p ositivity, and a disconnection with the overlying epithelial sheath essenti al for the movement of the dermal papilla, As a consequence, the hair bulb and dermal papilla remain stranded in the dermis, and indispensible message s between the dermal papilla and stem cells in the bulge are not transmitte d, so no further hair growth occurs. These findings suggest that the hairle ss gene product may play a crucial role in maintaining the delicate balance between cell proliferation, differentiation and apoptosis in the hair foll icle, as well as in the interfollicular epidermis.