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 shRNA 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.
Here, we examined the role of Tβ4 in developing and adult heart via 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.
Therefore, we conclude that Tβ4 is dispensable for embryonic viability, heart development, coronary vessel development and adult myocardial function.