title: Thymosin beta 4 is dispensable for murine cardiac development and function.
abstract: BACKGROUND
  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.
  
  
  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.affiliation: Department of Medicine, University of California-San Diego, La Jolla, 92093, USA.
authors.forename: Indroneal
authors.initials: I
authors.lastname: Banerjee
authors.forename: Jianlin
authors.initials: J
authors.lastname: Zhang
authors.forename: Thomas
authors.initials: T
authors.lastname: Moore-Morris
authors.forename: Stephan
authors.initials: S
authors.lastname: Lange
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Dalton
authors.forename: Yusu
authors.initials: Y
authors.lastname: Gu
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000196:embryology / Q000502:physiology; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000196:embryology* / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D013947:Thymosin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000099201:Thymosin beta(4)
chemical_list: D034741:RNA, Small Interfering; D013947:Thymosin; D000099201:Thymosin beta(4)