| Developmental cardiac hypertrophy in a mouse model of prolidase deficiency. | |
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MedLine Citation:
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PMID: 21472842 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Seungwoo Jung; Derek Silvius; Katherine A Nolan; Gregory L Borchert; Yoann H Millet; James M Phang; Teresa M Gunn |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-6 |
Journal Detail:
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Title: Birth defects research. Part A, Clinical and molecular teratology Volume: - ISSN: 1542-0760 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101155107 Medline TA: Birth Defects Res A Clin Mol Teratol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Department of Biomedical Sciences, Cornell University, Ithaca, New York. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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