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Thymosin beta 4 is dispensable for murine cardiac development and function.

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.

Pubmed ID: 22158707

Authors

  • Banerjee I
  • Zhang J
  • Moore-Morris T
  • Lange S
  • Shen T
  • Dalton ND
  • Gu Y
  • Peterson KL
  • Evans SM
  • Chen J

Journal

Circulation research

Publication Data

February 3, 2012

Associated Grants

  • Agency: NHLBI NIH HHS, Id: DP1 HL117649
  • Agency: NINDS NIH HHS, Id: P30 NS047101
  • Agency: NHLBI NIH HHS, Id: R01 HL066100
  • Agency: NHLBI NIH HHS, Id: R01 HL106968
  • Agency: NHLBI NIH HHS, Id: T32 HL007444

Mesh Terms

  • Animals
  • Coronary Vessels
  • Embryonic Development
  • Female
  • Gene Expression Regulation, Developmental
  • Heart
  • Male
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neovascularization, Physiologic
  • RNA, Small Interfering
  • Thymosin