Timeline of cardiac dystrophy in 3-18-month-old MDX mice.
The dystrophin-deficient (mdx) mouse remains the most commonly used model for Duchenne muscular dystrophy (DMD). Mdx mice show a predominantly covert cardiomyopathy, the hallmark of which is fibrosis. We compared mdx and normal mice at six ages (3, 6, 9, 12, 15, and 18 months) using in vivo assessment of cardiac function, selective collagen staining, and measures of TGF-β mRNA, Evans blue dye infiltration, macrophage infiltration, and aortic wall thickness. Clear temporal progression was demonstrated, including early fragility of cardiomyocyte membranes, which has an unrelated impact on cardiac function but is associated with macrophage infiltration and fibrosis. Aortic wall thickness is less in older mdx mice. Mdx mice display impaired responses to inotropic challenge from a young age; this is indicative of altered adrenoreceptor function. We draw attention to the paradox of ongoing fibrosis in mdx hearts without a strong molecular signature (in the form of TGF-β mRNA expression).
Van Erp
Christel
C
Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland, Australia.
Loch
David
D
Laws
Nicola
N
Trebbin
Andrea
A
Hoey
Andrew J
AJ
D000375:Aging; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D005070:Evans Blue / Q000493:pharmacokinetics; D005355:Fibrosis; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000150:complications*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics
D004396:Coloring Agents; D012333:RNA, Messenger; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D005070:Evans Blue