title: Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene, OCTN2.
abstract: The purpose of this study was to test whether heterozygotes of juvenile visceral steatosis mice, a model for systemic carnitine deficiency, may develop age-associated cardiomyopathy. Tissue morphological observations were carried out by light and electron microscopy to compare the heterozygous and age-matched control mice at periods of 1 and 2 years. Possible effects of the pathological mutation on lipid and glucose levels was also evaluated in humans and mice. Except mild increases in serum cholesterol levels in male heterozygous mice and humans, no changes were found in other factors, indicating that none of the confounding factors seems to be profound. Results demonstrated that heterozygous mice had larger left ventriclular myocyte diameters than the control mice. Morphological changes in cardiac muscles by electron microscopy revealed age-associated changes of lipid deposition and abnormal mitochondria in heterozygous mice. Two out of 60 heterozygous cohort and one out of nine heterozygous trim-kill mice had cardiac hypertrophy at ages older than 2 years. The present study and our previous work suggest that the carrier state of OCTN2 pathological mutations might be a risk factor for age-associated cardiomyopathy.
authors.affiliation: Department of Hygiene, Akita University School of Medicine, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Xiaofei
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Wada
authors.forename: Miwako
authors.initials: M
authors.lastname: Dakeishi
authors.forename: Fujiko
authors.initials: F
authors.lastname: Hirasawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Murata
authors.forename: Hirotake
authors.initials: H
authors.lastname: Masuda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nikaido
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D000328:Adult; D000375:Aging; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology*; D002331:Carnitine / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D009154:Mutation; D027701:Organic Cation Transport Proteins; D010084:Oxidation-Reduction; D000074058:Solute Carrier Family 22 Member 5; D015996:Survival Rate
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D005947:Glucose; D002331:Carnitine