Ornithine decarboxylase transgenic mice as a model for human atrichia withpapular lesions

The hair follicle is characterized by cyclic transformations from active gr owth and hair fiber production through regression into a resting phase. The growth phase, known as anagen, is associated with rapid rates of cell turn over, and variations in the rate of DNA synthesis in mouse skin throughout the hair cycle are accompanied by changes in the activity of ornithine deca rboxylase (ODC), a key enzyme in the synthesis of polyamines, which are act ively involved in regulation of normal cell division, differentiation, and growth. Previously, a transgenic mouse was created that overexpressed ODC i n the skin using a K6 promoter. The first hair cycle in neonatal transgenic mice appeared to be normal, but by the third week of postnatal life transg enic pups begin to progressively lose hair. The lower portion of the hair f ollicle was progressively replaced with enlarging cystic structures located in the deep dermis, and the transgenic mice exhibited excessive growth of skin mass resulting in pronounced wrinkling and folding. Interestingly, the se findings bore striking resemblance to the rhino mouse phenotype and to h uman patients with papular atrichia, a rare congenital ectodermal disorder characterized by progressive and irreversible hair loss in early childhood. The similarities in phenotype between transgenic mice and human atrichia w ith papular lesions suggest that ODC transgenics may represent a useful mod el for studying this disorder. It appears that ODC plays a functionally imp ortant, yet still obscure role in a complex metabolic pathway that is criti cal in hair follicle function not only in mice, but in humans as well.