| Thymosin beta 4 is dispensable for murine cardiac development and function. | |
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MedLine Citation:
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PMID: 22158707 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Thymosin beta 4 (Tβ4) is a 43-amino acid factor encoded by an X-linked gene. Recent studies have suggested that Tβ4 is a key factor in cardiac development, growth, disease, epicardial integrity, and blood vessel formation. Cardiac-specific short hairpin (sh)RNA knockdown of tβ4 has been reported to result in embryonic lethality at E14.5-16.5, with severe cardiac and angiogenic defects. However, this shRNA tβ4-knockdown model did not completely abrogate Tβ4 expression. To completely ablate Tβ4 and to rule out the possibility of off-target effects associated with shRNA gene silencing, further studies of global or cardiac-specific knockouts are critical. OBJECTIVE: We examined the role of Tβ4 in developing and adult heart through global and cardiac specific tβ4-knockout mouse models. METHODS AND RESULTS: Global tβ4-knockout mice were born at mendelian ratios and exhibited normal heart and blood vessel formation. Furthermore, in adult global tβ4-knockout mice, cardiac function, capillary density, expression of key cardiac fetal and angiogenic genes, epicardial marker expression, and extracellular matrix deposition were indistinguishable from that of controls. Tissue-specific tβ4-deficient mice, generated by crossing tβ4-floxed mice to Nkx2.5-Cre and αMHC-Cre, were also found to have no phenotype. CONCLUSIONS: We conclude that Tβ4 is dispensable for embryonic viability, heart development, coronary vessel development, and adult myocardial function. |
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Authors:
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Indroneal Banerjee; Jianlin Zhang; Thomas Moore-Morris; Stephan Lange; Tao Shen; Nancy D Dalton; Yusu Gu; Kirk L Peterson; Sylvia M Evans; Ju Chen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-08 |
Journal Detail:
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Title: Circulation research Volume: 110 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-03 Completed Date: 2012-04-20 Revised Date: 2013-05-13 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 456-64 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of California-San Diego, La Jolla, 92093, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Vessels / embryology, physiology Embryonic Development / drug effects Female Gene Expression Regulation, Developmental / drug effects Heart / embryology*, physiology* Male Mice Mice, Knockout Models, Animal Neovascularization, Physiologic / physiology RNA, Small Interfering / pharmacology Thymosin / deficiency, genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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DP1 HL117649/HL/NHLBI NIH HHS; P30 NS047101/NS/NINDS NIH HHS; R01 HL066100/HL/NHLBI NIH HHS; R01 HL106968/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 61512-21-8/Thymosin; 77591-33-4/thymosin beta(4) |
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