title: Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia.
abstract: Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in Drosophila melanogaster and 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). Ptc1 mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1 is a tumor suppressor. We previously identified a second mammalian Patched gene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping pattern with Shh in 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/tm1) mice. Our molecular analysis suggests that Ptc2(tm1) likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2(tm1/tm1) mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2(tm1/tm1) male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis.
authors.affiliation: Program in Developmental Biology, The Hospital for Sick Children, Toronto Medical Discovery Towers, MaRS Building, East Tower, Room 13-314, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Erica
authors.initials: E
authors.lastname: Nieuwenhuis
authors.forename: Jun
authors.initials: J
authors.lastname: Motoyama
authors.forename: Paul C
authors.initials: PC
authors.lastname: Barnfield
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Mo
authors.forename: Michael A
authors.initials: MA
authors.lastname: Crackower
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Hui
mesh_terms: D000505:Alopecia / Q000473:pathology*; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000196:embryology; D004622:Embryo, Mammalian / Q000166:cytology / Q000473:pathology; D005121:Extremities / Q000196:embryology; D005328:Fetal Viability; D018390:Gene Targeting; D018859:Hair Follicle / Q000166:cytology / Q000196:embryology / Q000473:pathology*; D053823:Hedgehog Proteins; D006965:Hyperplasia; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D013737:Testis / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C000606236:PTCH1 protein, human; C000606238:PTCH2 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; C000606240:Ptch1 protein, mouse; C000606241:Ptch2 protein, mouse; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1