Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in
Drosophila melanogasterand vertebrates. The Patched1( Ptc1) gene, encoding the Hh receptor, is mutated in nevoid basal cell carcinoma syndrome, a human genetic disorder associated with developmental abnormalities and increased incidences of basal cell carcinoma (BCC) and medulloblastoma (MB). Ptc1mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1is a tumor suppressor. We previously identified a second mammalian Patchedgene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2is expressed in an overlapping pattern with Shhin the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis. Here, we describe the generation and phenotypic analysis of Ptc2 tm1/tm1mice. Our molecular analysis suggests that Ptc2 tm1likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2during embryogenesis, Ptc2 tm1/tm1mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2 tm1/tm1male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2function is required for adult skin homeostasis.