Document Detail

Developmental cardiac hypertrophy in a mouse model of prolidase deficiency.
MedLine Citation:
PMID:  21472842     Owner:  NLM     Status:  Publisher    
BACKGROUND: Hypertrophic cardiomyopathy, characterized by thickened ventricular walls and reduced ventricular chamber volume, is a common cause of sudden cardiac death in young people. Most inherited forms result from mutations in genes encoding sarcomeric proteins. METHODS: Histologic analysis identified embryonic cardiac hypertrophy in dark-like mutant mice. BrdU analysis was performed to measure proliferation and cardiomyocytes were isolated to measure cell size. The dark-like mutation was identified by positional cloning. RESULTS: The dark-like mutation causes cardiomyocyte hypertrophy due to loss-of-function of peptidase d (Pepd), which encodes prolidase, a cytosolic enzyme that recycles proline for collagen re-synthesis. Prolidase deficiency is a rare autosomal recessive disease in humans with a broad phenotypic spectrum not reported to include heart defects, but a conserved role for prolidase in heart development was confirmed by morpholino knockdown in zebrafish. We tested the hypothesis that loss of prolidase function disrupts collagen-mediated integrin signaling and determined that the levels of several key integrin transducers were reduced in the hearts of dark-like mutant embryos. CONCLUSIONS: This work identifies dark-like mice as a model of prolidase deficiency that will be valuable for studying the role of proline metabolism in normal physiology and disease processes, and suggests that integrin signaling may regulate the onset of hypertrophic cardiac growth. Birth Defects Research (Part A) 2011. © 2011 Wiley-Liss, Inc.
Seungwoo Jung; Derek Silvius; Katherine A Nolan; Gregory L Borchert; Yoann H Millet; James M Phang; Teresa M Gunn
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-6
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  -     ISSN:  1542-0760     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Department of Biomedical Sciences, Cornell University, Ithaca, New York.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Relation of G1359A polymorphism of the cannabinoid receptor gene (CB1) with metabolic syndrome by AT...
Next Document:  Developmental toxicity of glyceryl trinitrate in quail embryos.