Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13, a gene coding for palmitoyl acyltransferase.
Abstract
Protein palmitoylation has emerged as an important mechanism for regulating protein
trafficking, stability, and protein-protein interactions; however, its relevance to
disease processes is not clear. Using a genome-wide, phenotype driven N-ethyl-N-nitrosourea-mediated
mutagenesis screen, we identified mice with failure to thrive, shortened life span,
skin and hair abnormalities including alopecia, severe osteoporosis, and systemic
amyloidosis (both AA and AL amyloids depositions). Whole-genome homozygosity mapping
with 295 SNP markers and fine mapping with an additional 50 SNPs localized the disease
gene to chromosome 7 between 53.9 and 56.3 Mb. A nonsense mutation (c.1273A>T)
was located in exon 12 of the Zdhhc13 gene (Zinc finger, DHHC domain containing 13),
a gene coding for palmitoyl transferase. The mutation predicted a truncated protein
(R425X), and real-time PCR showed markedly reduced Zdhhc13 mRNA. A second gene trap
allele of Zdhhc13 has the same phenotypes, suggesting that this is a loss of function
allele. This is the first report that palmitoyl transferase deficiency causes a severe
phenotype, and it establishes a direct link between protein palmitoylation and regulation
of diverse physiologic functions where its absence can result in profound disease
pathology. This mouse model can be used to investigate mechanisms where improper palmitoylation
leads to disease processes and to understand molecular mechanisms underlying human
alopecia, osteoporosis, and amyloidosis and many other neurodegenerative diseases
caused by protein misfolding and amyloidosis.
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https://hdl.handle.net/10161/4472Published Version (Please cite this version)
10.1371/journal.pgen.1000985Publication Info
Saleem, Amir N; Chen, Yen-Hui; Baek, Hwa Jin; Hsiao, Ya-Wen; Huang, Hong-Wen; Kao,
Hsiao-Jung; ... Chen, Yuan-Tsong (2010). Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13,
a gene coding for palmitoyl acyltransferase. PLoS genetics, 6(6). pp. e1000985. 10.1371/journal.pgen.1000985. Retrieved from https://hdl.handle.net/10161/4472.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yuan-Tsong Chen
Professor Emeritus of Pediatrics
Our overall research interests are in translational research. We aim at translating
the promise of genomic medicine into clinical reality. Specific projects at present
time include: 1). Identification of novel genes/targets associated with human diseases.
This includes susceptibility genes for common multi-factorial diseases and adverse
drug reactions. Genetic epidemiology, mouse ENU mutagenesis, bioinformatics and proteomics
are some approaches that we use in identif

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