Ornithine decarboxylase transgenic mice as a model for human atrichia with papular lesions.

Document Type

Article

Publication Date

2000

Keywords

Animal, Disease-Models-Animal, Hair-Follicle, Male, Mice, Mice-Inbred-HRS, Mice-Transgenic, Ornithine-Decarboxylase, Skin, Skin-Diseases, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

First Page

146

Last Page

151

JAX Source

Exp Dermatol 2000 Apr; 9(2):146-51.

Grant

CA34196/CA/NCI, AR43801/AR/NIAMS

Abstract

The hair follicle is characterized by cyclic transformations from active growth and hair fiber production through regression into a resting phase. The growth phase, known as anagen, is associated with rapid rates of cell turnover, and variations in the rate of DNA synthesis in mouse skin throughout the hair cycle are accompanied by changes in the activity of ornithine decarboxylase (ODC), a key enzyme in the synthesis of polyamines, which are actively involved in regulation of normal cell division, differentiation, and growth. Previously, a transgenic mouse was created that overexpressed ODC in 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 transgenic pups begin to progressively lose hair. The lower portion of the hair follicle 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, these findings bore striking resemblance to the rhino mouse phenotype and to human 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 with papular lesions suggest that ODC transgenics may represent a useful model for studying this disorder. It appears that ODC plays a functionally important, yet still obscure role in a complex metabolic pathway that is critical in hair follicle function not only in mice, but in humans as well.

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