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Cardiomyocyte ultrastructural damage in β-thalassaemic mice
Chanita Sanyear1, Punnee Butthep, Ramaneeya Nithipongvanich
1Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Phuttamonthon, Thailand.
Insights
This study evaluated heart pathology in mouse models of beta-thalassaemia. The R mouse model, exhibiting iron overload, showed progressive cardiac ultrastructural damage, making it suitable for studying thalassaemic heart disease.
Area of Science:
- Cardiovascular Pathology
- Hematology
- Genetics
Background:
- Beta-thalassaemia causes hereditary anemia due to reduced beta-globin production.
- Cardiac complications from iron overload are the primary cause of mortality in beta-thalassaemia patients.
Purpose of the Study:
- To evaluate cardiac pathology in various beta-thalassaemia mouse models using light and electron microscopy.
- To identify a suitable animal model for in vivo studies of thalassaemic heart disease.
Main Methods:
- Utilized thalassaemic mice with specific human beta-thalassaemia mutations (IVSII-654) and beta(E)-globin transgenes.
- Employed light and electron microscopy to examine cardiac myocyte pathology.
- Compared wild-type mice with genetically modified thalassaemic mouse models (654, E4, 654/E4, and R).
Main Results:
- Iron deposition was observed in cardiac myocytes of 654 and R mice.
- Ultrastructural cardiac damage, including mitochondrial swelling and myofilament loss, was evident exclusively in R mice.
- Histopathological changes in R mice cardiomyocytes correlated with increased tissue iron levels.
Conclusions:
- The R thalassaemic mouse model exhibits progressive cardiac ultrastructural pathology consistent with human thalassaemia.
- This model is suitable for in vivo pathophysiological studies of the thalassaemic heart.
- Findings highlight the critical role of iron overload in cardiac damage in beta-thalassaemia.
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.
