Iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood

PeerJ

article

Chanita Sanyear¹  Punnee Butthep¹  Wiraya Eamsaard²  Suthat Fucharoen³  Saovaros Svasti³  Patarabutr Masaratana² 

[1]Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

[2]Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University

[3]Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University

关键词: Heterozygous β-globin knockout mice;    Hepcidin;    Age;    Thalassemia;    Iron transporters;   

DOI  :  10.7717/peerj.8802

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background Iron overload is one of common complications of β-thalassemia. Systemic iron homeostasis is regulated by iron-regulatory hormone, hepcidin, which inhibits intestinal iron absorption and iron recycling by reticuloendothelial system. In addition, body iron status and requirement can be altered with age. In adolescence, iron requirement is increased due to blood volume expansion and growth spurt. Heterozygous β-globin knockout mice (Hbbth3/+; BKO) is a mouse model of thalassemia widely used to study iron homeostasis under this pathological condition. However, effects of age on iron homeostasis, particularly the expression of genes involved in hemoglobin metabolism as well as erythroid regulators in the spleen, during adolescence have not been explored in this mouse model. Methods Iron parameters as well as the mRNA expression of hepcidin and genes involved in iron transport and metabolism in wildtype (WT) and BKO mice during adolescence (6–7 weeks old) and adulthood (16–20 weeks old) were analyzed and compared by 2-way ANOVA. Results The transition of adolescence to adulthood was associated with reductions in duodenal iron transporter mRNA expression and serum iron levels of both WT and BKO mice. Erythrocyte parameters in BKO mice remained abnormal in both age groups despite persistent induction of genes involved in hemoglobin metabolism in the spleen and progressively increased extramedullary erythropiesis. In BKO mice, adulthood was associated with increased liver hepcidin and ferroportin mRNA expression along with splenic erythroferrone mRNA suppression compared to adolescence. Conclusion Our results demonstrate that iron homeostasis in a mouse model of thalassemia intermedia is altered between adolescence and adulthood. The present study underscores the importance of the age of thalassemic mice in the study of molecular or pathophysiological changes under thalassemic condition.

【 授权许可】

CC BY