title: Cardiomyocyte ultrastructural damage in β-thalassaemic mice.
abstract: β-thalassaemia is a hereditary anaemia resulting from the absence or reduction in β-globin chain production. Heart complications related to iron overload are the most serious cause of death in these patients. In this report cardiac pathology of β-thalassaemic mice was evaluated by light and electron microscopy. The study was carried out in thalassaemic mice carrying human β-thalassaemia mutation, IVSII-654 (654), transgenic mice carrying human β(E) -globin transgene insertion (E4), thalassaemic mice with human β(E) -globin transgene insertion (654/E4) and homozygous thalassaemic mice rescued by the human β(E) -globin transgene (R), which is generated by cross-breeding between the 654 and E4 mice. Histology showed iron deposition in cardiac myocytes of 654 and R mice, but the ultrastructural damage was observed only in the R mice when compared with the wild type, 654, E4 and 654/E4 mice. Histopathological changes in the cardiomyocytes of the R mice included mitochondrial swelling, loss of myofilaments and the presence of lipofuscin, related to the increased level of tissue iron content. The progressive ultrastructural pathology in R mice cardiomyocytes is consistent with the ultrastructural pathology previously studied in patients with thalassaemia. Thus, this R thalassaemic mouse model is suitable for in vivo pathophysiological study of thalassaemic heart.
authors.affiliation: Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Phuttamonthon, Thailand.
authors.forename: Chanita
authors.initials: C
authors.lastname: Sanyear
authors.forename: Punnee
authors.initials: P
authors.lastname: Butthep
authors.forename: Ramaneeya
authors.initials: R
authors.lastname: Nithipongvanich
authors.forename: Pornpan
authors.initials: P
authors.lastname: Sirankapracha
authors.forename: Pranee
authors.initials: P
authors.lastname: Winichagoon
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Saovaros
authors.initials: S
authors.lastname: Svasti
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000648:ultrastructure*; D009210:Myofibrils / Q000648:ultrastructure; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics / Q000473:pathology*
chemical_list: D055544:beta-Globins
keywords: cardiomyocytes; thalassaemic mice; ultrastructural pathology
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