title: SWI/SNF complexes containing Brahma or Brahma-related gene 1 play distinct roles in smooth muscle development.
abstract: SWI/SNF ATP-dependent chromatin-remodeling complexes containing either Brahma-related gene 1 (Brg1) or Brahma (Brm) play important roles in mammalian development. In this study we examined the roles of Brg1 and Brm in smooth muscle development, in vivo, through generation and analysis of mice harboring a smooth muscle-specific knockout of Brg1 on wild-type and Brm null backgrounds. Knockout of Brg1 from smooth muscle in Brg1(flox/flox) mice expressing Cre recombinase under the control of the smooth muscle myosin heavy-chain promoter resulted in cardiopulmonary defects, including patent ductus arteriosus, in 30 to 40% of the mice. Surviving knockout mice exhibited decreased expression of smooth muscle-specific contractile proteins in the gastrointestinal tract, impaired contractility, shortened intestines, disorganized smooth muscle cells, and an increase in apoptosis of intestinal smooth muscle cells. Although Brm knockout mice had normal intestinal structure and function, knockout of Brg1 on a Brm null background exacerbated the effects of knockout of Brg1 alone, resulting in an increase in neonatal lethality. These data show that Brg1 and Brm play critical roles in regulating development of smooth muscle and that Brg1 has specific functions within vascular and gastrointestinal smooth muscle that cannot be performed by Brm.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5120, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.forename: Ju-Ryoung
authors.initials: JR
authors.lastname: Kim
authors.forename: Jiliang
authors.initials: J
authors.lastname: Zhou
authors.forename: Rebekah E
authors.initials: RE
authors.lastname: Jones
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
authors.forename: Ghassan S
authors.initials: GS
authors.lastname: Kassab
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Shawn
authors.initials: S
authors.lastname: Ahlfeld
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: B Paul
authors.initials: BP
authors.lastname: Herring
mesh_terms: D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics / Q000473:pathology; D007422:Intestines / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D009130:Muscle, Smooth / Q000196:embryology*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D013270:Stomach / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D009687:Nuclear Proteins; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases