title: Limitations of the MRL mouse as a model for cardiac regeneration.
abstract: OBJECTIVE
  Myocardial repair following injury in mammals is restricted such that damaged areas are replaced by scar tissue, impairing cardiac function. MRL mice exhibit exceptional regenerative healing in an ear punch wound model. Some myocardial repair with restoration of heart function has also been reported following cryoinjury. Increased cardiomyocyte proliferation and a foetal liver stem cell population were implicated. We investigated molecular mechanisms facilitating myocardial repair in MRL mice to identify potential therapeutic targets in non-regenerative species.
  
  
  METHODS
  Expressions of specific cell-cycle regulators that might account for regeneration (CDKs 1, 2, 4 and 6; cyclins A, E, D1 and B1; p21, p27 and E2F5) were compared by immunoblotting in MRL and control C57BL/6 ventricles during development. Flow cytometry was used to investigate stem cell populations in livers from foetal mice, and infarct sizes were compared in coronary artery-ligated and sham-treated MRL and C57BL/6 adult mice.
  
  
  RESULTS
  No differences in the expressions of cell cycle regulators were observed between the two strains. Expressions of CD34+Sca1+ckit-, CD34+Sca1+ckit+ and CD34+Sca1-ckit+ increased in livers from C57BL/6 vs MRL mice. No differences were observed in infarct sizes, levels of fibrosis, Ki67 staining or cardiac function between MRL and C57BL/6 mice.
  
  
  CONCLUSIONS
  No intrinsic differences were observed in cell cycle control molecules or stem cell populations between MRL and control C57BL mouse hearts. Pathophysiologically relevant ischaemic injury is not repaired more efficiently in MRL myocardium, questioning the use of the MRL mouse as a reliable model for cardiac regeneration in response to pathophysiologically relevant forms of injury.
authors.affiliation: School of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire, UK.
authors.forename: Fleur L
authors.initials: FL
authors.lastname: Moseley
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Faircloth
authors.forename: Wendy
authors.initials: W
authors.lastname: Lockwood
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marber
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Bicknell
authors.forename: Petr
authors.initials: P
authors.lastname: Valasek
authors.forename: Gavin
authors.initials: G
authors.lastname: Brooks
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006321:Heart / Q000502:physiology*; D008099:Liver / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D018844:Cyclin-Dependent Kinases