title: Disruption of striated preferentially expressed gene locus leads to dilated cardiomyopathy in mice.
abstract: BACKGROUND
  The striated preferentially expressed gene (Speg) generates 4 different isoforms through alternative promoter use and tissue-specific splicing. Depending on the cell type, Speg isoforms may serve as markers of striated or smooth muscle differentiation.
  
  
  RESULTS
  To elucidate function of Speg gene isoforms, we disrupted the Speg gene locus in mice by replacing common exons 8, 9, and 10 with a lacZ gene. beta-Galactosidase activity was detected in cardiomyocytes of the developing heart starting at day 11.5 days post coitum (dpc). beta-Galactosidase activity in other cell types, including vascular smooth muscle cells, did not begin until 18.5 dpc. In the developing heart, protein expression of only Spegalpha and Spegbeta isoforms was present in cardiomyocytes. Homozygous Speg mutant hearts began to enlarge by 16.5 dpc, and by 18.5 dpc, they demonstrated dilation of right and left atria and ventricles. These cardiac abnormalities in the absence of Speg were associated with a cellular hypertrophic response, myofibril degeneration, and a marked decrease in cardiac function. Moreover, Speg mutant mice exhibited significant neonatal mortality, with increased death occurring by 2 days after birth.
  
  
  CONCLUSIONS
  These findings demonstrate that mutation of the Speg locus leads to cardiac dysfunction and a phenotype consistent with a dilated cardiomyopathy.
authors.affiliation: Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Tripurasundari
authors.initials: T
authors.lastname: Ramjiganesh
authors.forename: Yen-Hsu
authors.initials: YH
authors.lastname: Chen
authors.forename: Su Wol
authors.initials: SW
authors.lastname: Chung
authors.forename: Sean R
authors.initials: SR
authors.lastname: Hall
authors.forename: Scott L
authors.initials: SL
authors.lastname: Schissel
authors.forename: Robert F
authors.initials: RF
authors.lastname: Padera
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
authors.forename: Kate G
authors.initials: KG
authors.lastname: Ackerman
authors.forename: Jan
authors.initials: J
authors.lastname: Kajstura
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.forename: Shaw-Fang
authors.initials: SF
authors.lastname: Yet
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Layne
authors.forename: Mark A
authors.initials: MA
authors.lastname: Perrella
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D018390:Gene Targeting; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009219:Myosin-Light-Chain Kinase / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; C484400:Speg protein, mouse; D009219:Myosin-Light-Chain Kinase