Document Detail


Thymosin beta 4 is dispensable for murine cardiac development and function.
MedLine Citation:
PMID:  22158707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-08
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-03     Completed Date:  2012-04-20     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  456-64     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of California-San Diego, La Jolla, 92093, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
0/RNA, Small Interfering; 61512-21-8/Thymosin; 77591-33-4/thymosin beta(4)
Comments/Corrections

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