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

ABSTRACT: Thymosin beta 4 (T?4) is a 43-amino acid factor encoded by an X-linked gene. Recent studies have suggested that T?4 is a key factor in cardiac development, growth, disease, epicardial integrity, and blood vessel formation. Cardiac-specific short hairpin (sh)RNA knockdown of t?4 has been reported to result in embryonic lethality at E14.5-16.5, with severe cardiac and angiogenic defects. However, this shRNA t?4-knockdown model did not completely abrogate T?4 expression. To completely ablate T?4 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.We examined the role of T?4 in developing and adult heart through global and cardiac specific t?4-knockout mouse models.Global t?4-knockout mice were born at mendelian ratios and exhibited normal heart and blood vessel formation. Furthermore, in adult global t?4-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 t?4-deficient mice, generated by crossing t?4-floxed mice to Nkx2.5-Cre and ?MHC-Cre, were also found to have no phenotype.We conclude that T?4 is dispensable for embryonic viability, heart development, coronary vessel development, and adult myocardial function.

SUBMITTER: Banerjee I 

PROVIDER: S-EPMC3739283 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature