Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous Mouse Mutation in the Palmitoyl Transferase Zdhhc13 Gene
| Autor: | John DiGiovanni, Gyu Song, Lars Mecklenburg, Alexsandra Espejo, Richard D. Wood, Jean Louis Guénet, Jean Jaubert, Marcela Del Rio, Donna F. Kusewitt, Claudio J. Conti, Fernando Benavides, Lucía Martínez-Santamaría, Sharon Y.R. Dent, Eleonora Napoli, Cecilia R Giulivi, Carlos J. Perez, Brian M. Iritani, Mark T. Bedford |
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| Přispěvatelé: | Department of Epigenetics and Molecular Carcinogenesis [Texas], The University of Texas M.D. Anderson Cancer Center [Houston], Mecklenburg-consulting [Hamburg, Germany], Génétique de la souris - Mouse Genetics, Institut Pasteur [Paris], Centro de Investigaciones Energéticas Medioambientales y Tecnológicas [Madrid] (CIEMAT), Universidad Carlos III de Madrid [Madrid] (UC3M), CIBER de Enfermedades Raras (CIBERER), Instituto de Investigación Sanitaria Fundación Jiménez Diaz [Madrid] (IIS-FJD), Universidad Autonoma de Madrid (UAM)-Fundacion Jimenez Diaz [Madrid] (FJD), Department of Comparative Medicine, University of Washington [Seattle], School of Veterinary Medicine [UC Davis], University of California [Davis] (UC Davis), University of California-University of California, Dell Pediatric Research Institute [Austin], University of Texas at Austin [Austin], Medical Investigations of Neurodevelopmental Disorders Institute [Sacramento] (MIND Institute), University of California-University of California-UC Davis Health [Sacramento], Graduate School of Biomedical Sciences [Houston], The University of Texas Health Science Center at Houston (UTHealth)-The University of Texas M.D. Anderson Cancer Center [Houston], Génétique fonctionnelle de la Souris, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Baker Foundation Pilot Project to FB, by the 'Youth Excellence scholarship' from Caja de Burgos to LM, by the CHDI Foundation (A-2638 & A-4489) to CG, and by the National Institutes of Health (NIH) Grant CA132840 from the National Cancer Institute and the Grady F. Saunders, PhD Distinguished Professorship to RDW., We thank the Research Animal Support Facility-Smithville for their assistance with the maintenance of the mouse strains, the Histology and Tissue Processing Facility Core for processing the samples, the Molecular Biology Facility Core for DNA sequencing, and Kevin Lin for statistical analyses. We also acknowledge Sarah Adai for proofreading the manuscript. This study made use of the Research Animal Support Facility-Smithville (including Genetic Services and Mutant Mouse Pathology Services), the Bone Histomorphometry Core, and the High Resolution Electron Microscopy Facility (HREMF), which are supported by P30 CA016672 DHHS/NCI Cancer Center Support Grant to MD Anderson Cancer Center. This study also made use of the RNA In Situ Hybridization Core at Baylor College of Medicine, Houston, TX, which is, in part, supported by a Shared Instrumentation grant from the NIH (1S10OD016167)., Institut Pasteur [Paris] (IP), Universidad Autónoma de Madrid (UAM)-Fundacion Jimenez Diaz [Madrid] (FJD), School of Veterinary Medicine [Univ California Davis] (VetMed - UC Davis), University of California (UC)-University of California (UC), University of California (UC)-University of California (UC)-UC Davis Health [Sacramento], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2015 |
| Předmět: |
Keratinocytes
Pathology Skin Neoplasms Mutant MESH: Codon Terminator MESH: Epidermal Cells medicine.disease_cause Biochemistry MESH: Acyltransferases / genetics MESH: Keratinocytes / physiology Mice 0302 clinical medicine Hair cycle MESH: Animals Palmitoyl acyltransferase 0303 health sciences integumentary system NF-kappa B 3. Good health Phenotype medicine.anatomical_structure Neutrophil Infiltration 030220 oncology & carcinogenesis Codon Terminator Keratinocyte medicine.medical_specialty Clinical Sciences Oncology and Carcinogenesis Dermatology Biology MESH: Phenotype MESH: Skin Neoplasms / etiology Article MESH: Skin Neoplasms / genetics 03 medical and health sciences MESH: Genetic Predisposition to Disease medicine Animals Genetic Predisposition to Disease Terminator MESH: NF-kappa B / physiology Codon MESH: Mice Molecular Biology 030304 developmental biology Epidermis (botany) Dermatology & Venereal Diseases MESH: Leukocyte Elastase / metabolism Cell Biology MESH: Bromodeoxyuridine / metabolism NFKB1 Molecular biology MESH: Neutrophil Infiltration [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics Bromodeoxyuridine Epidermal Cells Mutation NIH 3T3 Cells MESH: Mutation Leukocyte Elastase Carcinogenesis DHHC domain Acyltransferases MESH: NIH 3T3 Cells |
| Zdroj: | Journal of Investigative Dermatology Journal of Investigative Dermatology, Nature Publishing Group, 2015, 135 (12), pp.3133-3143. ⟨10.1038/jid.2015.314⟩ The Journal of investigative dermatology The Journal of investigative dermatology, vol 135, iss 12 Journal of Investigative Dermatology, 2015, 135 (12), pp.3133-3143. ⟨10.1038/jid.2015.314⟩ |
| ISSN: | 0022-202X 1523-1747 |
| Popis: | International audience; Here we describe a spontaneous mutation in the Zdhhc13 (zinc finger, DHHC domain containing 13) gene (also called Hip14l), one of 24 genes encoding palmitoyl acyltransferase (PAT) enzymes in the mouse. This mutation (Zdhhc13luc) was identified as a nonsense base substitution, which results in a premature stop codon that generates a truncated form of the ZDHHC13 protein, representing a potential loss-of-function allele. Homozygous Zdhhc13luc/Zdhhc13luc mice developed generalized hypotrichosis, associated with abnormal hair cycle, epidermal and sebaceous gland hyperplasia, hyperkeratosis, and increased epidermal thickness. Increased keratinocyte proliferation and accelerated transit from basal to more differentiated layers were observed in mutant compared with wild-type (WT) epidermis in untreated skin and after short-term 12-O-tetradecanoyl-phorbol-13-acetate treatment and acute UVB exposure. Interestingly, this epidermal phenotype was associated with constitutive activation of NF-κB (RelA) and increased neutrophil recruitment and elastase activity. Furthermore, tumor multiplicity and malignant progression of papillomas after chemical skin carcinogenesis were significantly higher in mutant mice than WT littermates. To our knowledge, this is the first report of a protective role for PAT in skin carcinogenesis. |
| Databáze: | OpenAIRE |
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