Thymosin Beta 4 Is Dispensable for Murine Cardiac Development and Function

• Published in: Circulation research Vol. 110; no. 3; pp. 456 - 464
• Main Authors: Banerjee, Indroneal, Zhang, Jianlin, Moore-Morris, Thomas, Lange, Stephan, Shen, Tao, Dalton, Nancy D, Gu, Yusu, Peterson, Kirk L, Evans, Sylvia M, Chen, Ju
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 03.02.2012; Lippincott Williams & Wilkins
• Subjects: Animals; Biological and medical sciences; Coronary Vessels - embryology; Coronary Vessels - physiology; Embryonic Development - drug effects; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental - drug effects; Heart - embryology; Heart - physiology; Male; Mice; Mice, Knockout; Models, Animal; Neovascularization, Physiologic - physiology; RNA, Small Interfering - pharmacology; Thymosin - deficiency; Thymosin - genetics; Thymosin - physiology; Vertebrates: cardiovascular system; Vertebrata; Mammalia; Development; Epicardium; Thymosin; cardiac function; thymosin beta 4; Circulatory system; Thymus hormone; cardiac development; Pentapeptide
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.111.258616

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.