Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia.
- Authors
- Nieuwenhuis, Erica; Motoyama, Jun; Barnfield, Paul C; Yoshikawa, Yoshiaki; Zhang, Xiaoyun; Mo, Rong; Crackower, Michael A; Hui, Chi-Chung
- Year
- 2006
- Journal
- Molecular and cellular biology
- PMID
- 16914743
- DOI
- 10.1128/MCB.00295-06
- PMCID
- PMC1592833
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.
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| Title | Year | PMID |
|---|---|---|
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Desert Hedgehog mediates stem Leydig cell differentiation through Ptch2/Gli1/Sf1 signaling axis | Zhao C et al. | β | 2025 | β |
| Genome-wide scans for signatures of selection in North African sheep reveals differentially selected regions between fat- and thin-tailed breeds. | Ben-Jemaa S et al. | β | 2025 | β |
| Sonic hedgehog signaling in craniofacial development. | Xu J et al. | β | 2023 | β |
| Hedgehog signaling. | Ingham PW | β | 2022 | β |
| O-GlcNAcylation promotes cerebellum development and medulloblastoma oncogenesis via SHH signaling. | Chen L et al. | β | 2022 | β |
| Ptch2 is a Potential Regulator of Mesenchymal Stem Cells. | Juuri E et al. | β | 2022 | β |
| Mouse Ptchd3 is a non-essential gene. | GonzΓ‘lez Morales SR et al. | β | 2020 | β |
| Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration. | Kim Y et al. | β | 2020 | β |
| A healthy individual with a homozygous <i>PTCH2</i> frameshift variant: Are variants of <i>PTCH2</i> associated with nevoid basal cell carcinoma syndrome? | Altaraihi M et al. | β | 2019 | β |
| Biochemical mechanisms of vertebrate hedgehog signaling. | Kong JH et al. | β | 2019 | β |
| Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche. | Binder M et al. | β | 2019 | β |
| Hedgehog Signal and Genetic Disorders. | Sasai N et al. | β | 2019 | β |
| Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction. | Sheybani-Deloui S et al. | β | 2018 | β |
| Patched-2 functions to limit Patched-1 deficient skin cancer growth. | Veenstra VL et al. | β | 2018 | β |
| The protein-specific activities of the transmembrane modules of Ptch1 and Ptch2 are determined by their adjacent protein domains. | Fleet AJ et al. | β | 2018 | β |
| Multi-layered mutation in hedgehog-related genes in Gorlin syndrome may affect the phenotype. | Onodera S et al. | β | 2017 | β |
| Roles of the Hedgehog Signaling Pathway in Epidermal and Hair Follicle Development, Homeostasis, and Cancer. | Abe Y et al. | β | 2017 | β |
| TGF-Ξ² receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis. | Gencer S et al. | β | 2017 | β |
| The Multiple Roles of FGF Signaling in the Developing Spinal Cord. | Diez Del Corral R et al. | β | 2017 | β |
| FGF signaling enhances a sonic hedgehog negative feedback loop at the initiation of spinal cord ventral patterning. | Morales AV et al. | β | 2016 | β |
| Hedgehog receptor function during craniofacial development. | Xavier GM et al. | β | 2016 | β |
| Regulation of Hedgehog Signalling Inside and Outside the Cell. | Ramsbottom SA et al. | β | 2016 | β |
| Ptch2 shares overlapping functions with Ptch1 in Smo regulation and limb development. | Zhulyn O et al. | β | 2015 | β |
| Regulation of Hedgehog signaling by ubiquitination. | Hsia EY et al. | β | 2015 | β |
| Secreted HHIP1 interacts with heparan sulfate and regulates Hedgehog ligand localization and function. | Holtz AM et al. | β | 2015 | β |
| Evasion of p53 and G2/M checkpoints are characteristic of Hh-driven basal cell carcinoma. | Li ZJ et al. | β | 2014 | β |
| Patched 1 and patched 2 redundancy has a key role in regulating epidermal differentiation. | Adolphe C et al. | β | 2014 | β |
| Ptch2 mediates the Shh response in Ptch1-/- cells. | Alfaro AC et al. | β | 2014 | β |
| Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia. | Rogler LE et al. | β | 2014 | β |
| Essential role for ligand-dependent feedback antagonism of vertebrate hedgehog signaling by PTCH1, PTCH2 and HHIP1 during neural patterning. | Holtz AM et al. | β | 2013 | β |
| Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome. | Fujii K et al. | β | 2013 | β |
| Is PATCHED an important candidate gene for neural tube defects? Cranial and thoracic neural tube defects in a family with Gorlin syndrome: a case report. | Roudgari H et al. | β | 2012 | β |
| Kif7 regulates Gli2 through Sufu-dependent and -independent functions during skin development and tumorigenesis. | Li ZJ et al. | β | 2012 | β |
| Clinical implications of hedgehog signaling pathway inhibitors. | Liu H et al. | β | 2011 | β |
| Role of epidermal primary cilia in the homeostasis of skin and hair follicles. | Croyle MJ et al. | β | 2011 | β |
| Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. | Yang L et al. | β | 2010 | β |
| Cellular signaling pathways regulating the initial stage of adipogenesis and marbling of skeletal muscle. | Du M et al. | β | 2010 | β |
| Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability. | Noor A et al. | β | 2010 | β |
| Hedgehog signaling in the normal and neoplastic mammary gland. | Visbal AP et al. | β | 2010 | β |
| Hedgehog signaling update. | Cohen MM | β | 2010 | β |
| Expression of Patched-1 and Smoothened in testicular meiotic and post-meiotic cells. | Morales CR et al. | β | 2009 | β |
| Hedgehog signalling: emerging evidence for non-canonical pathways. | Jenkins D | β | 2009 | β |
| Hereditary hair loss and the ancient signaling pathways that regulate ectodermal appendage formation. | Van Raamsdonk CD | β | 2009 | β |
| A missense mutation in PTCH2 underlies dominantly inherited NBCCS in a Chinese family. | Fan Z et al. | β | 2008 | β |
| Dose-dependent requirement of patched homologue 1 in mouse pancreatic beta cell mass. | Nakayama S et al. | β | 2008 | β |
| Exclusion of patched homolog 2 (PTCH2) as a candidate gene for alopecia X in Pomeranians and Keeshonden. | Mausberg EM et al. | β | 2008 | β |
| Hedgehog: functions and mechanisms. | Varjosalo M et al. | β | 2008 | β |
| Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. | Omenetti A et al. | β | 2008 | β |
| Impaired skin and hair follicle development in Runx2 deficient mice. | Glotzer DJ et al. | β | 2008 | β |
| Implications of hedgehog signaling antagonists for cancer therapy. | Xie J | β | 2008 | β |
| Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1. | Nieuwenhuis E et al. | β | 2007 | β |
| Hedgehog is involved in prostate basal cell hyperplasia formation and its progressing towards tumorigenesis. | Chen BY et al. | β | 2007 | β |