title: Varying susceptibility to myocardial infarction among C57BL/6 mice of different genetic background.
abstract: Genetically manipulated mouse lines are invaluable to investigate the effects of a single gene on sensitivity to ischemia. When choosing appropriate controls, we were concerned that intrinsic, strain-independent but colony-dependent differences may influence the susceptibility to ischemia. We, therefore, compared the infarct:risk volume ratio (I:R%) after 30-min global ischemia in Langendorff-perfused hearts from outbred C57BL/6 mice with that in wild-type mice derived from heterozygote x heterozygote crosses of two different in-house C57BL/6 mouse lines with targeted disruption of an MKK3 or MAPKAPK2 allele. Despite similar hemodynamic characteristics, I:R% in outbred C57BL/6 hearts was significantlysmaller (40.8 +/- 2.8%) than in C57BL/6 MAPKAPK2 wild types (65.8 +/- 4.5%, P = 0.0003) and significantly larger than in C57BL/6 MKK3 wild types (23.7 +/- 2.9%, P = 0.002). Therefore, inherent colony substrain-dependent differences appear to influence the susceptibility to infarction in response to global ischemia, underscoring the importance of using colony-matched wild-type controls in murine studies of myocardial ischemia.
authors.affiliation: Department of Cardiology, KCL, The Rayne Institute, St. Thomas' Hospital, SE1 7EH, London, UK.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Gorog
authors.forename: Masaya
authors.initials: M
authors.lastname: Tanno
authors.forename: Alamgir M N
authors.initials: AM
authors.lastname: Kabir
authors.forename: Gajen S
authors.initials: GS
authors.lastname: Kanaganayagam
authors.forename: Rekha
authors.initials: R
authors.lastname: Bassi
authors.forename: Simon G
authors.initials: SG
authors.lastname: Fisher
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marber
mesh_terms: D000483:Alleles; D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D047908:Intracellular Signaling Peptides and Proteins; D048371:MAP Kinase Kinase 3; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics*; D010477:Perfusion; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D013045:Species Specificity; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D048371:MAP Kinase Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C482531:Map2k3 protein, mouse