Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous Mouse Mutation in the Palmitoyl Transferase Zdhhc13 Gene

6533b839fe1ef96bd12a662a

RESEARCH PRODUCT

Increased Susceptibility to Skin Carcinogenesis Associated with a Spontaneous Mouse Mutation in the Palmitoyl Transferase Zdhhc13 Gene

John Digiovanni Gyu Song Lars Mecklenburg Alexsandra Espejo Richard D. Wood Richard D. Wood Jean Louis Guénet Jean Jaubert Marcela Del Rio Donna F. Kusewitt Donna F. Kusewitt Claudio J. Conti Claudio J. Conti Claudio J. Conti Fernando Benavides Fernando Benavides Lucía Martínez-santamaría Sharon Y.r. Dent Sharon Y.r. Dent Eleonora Napoli Cecilia R Giulivi Carlos J. Perez Brian M. Iritani Mark T. Bedford Mark T. Bedford

subject

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

description

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.

year	journal	country	edition	language
2015-12-01	Journal of Investigative Dermatology

https://doi.org/10.1038/jid.2015.314