title: The superhealing MRL background improves muscular dystrophy.
abstract: BACKGROUND
  Mice from the MRL or "superhealing" strain have enhanced repair after acute injury to the skin, cornea, and heart. We now tested an admixture of the MRL genome and found that it altered the course of muscle pathology and cardiac function in a chronic disease model of skeletal and cardiac muscle. Mice lacking γ-sarcoglycan (Sgcg), a dystrophin-associated protein, develop muscular dystrophy and cardiomyopathy similar to their human counterparts with limb girdle muscular dystrophy. With disruption of the dystrophin complex, the muscle plasma membrane becomes leaky and muscles develop increased fibrosis.
  
  
  METHODS
  MRL/MpJ mice were bred with Sgcg mice, and cardiac function was measured. Muscles were assessed for fibrosis and membrane leak using measurements of hydroxyproline and Evans blue dye. Quantitative trait locus mapping was conducted using single nucleotide polymorphisms distinct between the two parental strains.
  
  
  RESULTS
  Introduction of the MRL genome reduced fibrosis but did not alter membrane leak in skeletal muscle of the Sgcg model. The MRL genome was also associated with improved cardiac function with reversal of depressed fractional shortening and the left ventricular ejection fraction. We conducted a genome-wide analysis of genetic modifiers and found that a region on chromosome 2 was associated with cardiac, diaphragm muscle and abdominal muscle fibrosis.
  
  
  CONCLUSIONS
  These data are consistent with a model where the MRL genome acts in a dominant manner to suppress fibrosis in this chronic disease setting of heart and muscle disease.
authors.affiliation: Department of Medicine, Section of Cardiology, 5841 S, Maryland, MC 6088, Chicago, IL, 60637, USA. emcnally@uchicago.edu.
authors.forename: Ahlke
authors.initials: A
authors.lastname: Heydemann
authors.forename: Kayleigh A
authors.initials: KA
authors.lastname: Swaggart
authors.forename: Gene H
authors.initials: GH
authors.lastname: Kim
authors.forename: Jenan
authors.initials: J
authors.lastname: Holley-Cuthrell
authors.forename: Michele
authors.initials: M
authors.lastname: Hadhazy
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McNally