OVEREXPRESSION OF PARATHYROID HORMONE-RELATED PROTEIN IN THE SKIN OF TRANSGENIC MICE INTERFERES WITH HAIR FOLLICLE DEVELOPMENT

Parathyroid hormone-related peptide (PTHrP) was initially discovered a s the cause of the syndrome of humoral hypercalcemia of malignancy. Su bsequently, the PTHrP gene has been shown to be expressed in a wide va riety of normal tissues, including skin. Because the biological functi on of PTHrP in skin remains unknown, we used the human keratin 14 prom oter to target overexpression of PTHrP to the skin of transgenic mice. We achieved a 10-fold level of overexpression in skin, and human kera tin 14 promoter-PTHrP transgenic mice displayed a disturbance in norma l hair follicle development. These mice either failed to initiate foll icle development or showed a delay in the initiation of follicles. The se findings suggest that PTHrP normally plays a role in the early stag es of hair follicle development and support previous speculation that the peptide may function in regulating cellular differentiation.