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Exp Ther Med. 2018 Feb;15(2):1449-1455. doi: 10.3892/etm.2017.5523. Epub 2017 Nov 17.

A composite mouse model of aplastic anemia complicated with iron overload.

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Department of Hematology, First Affiliated Hospital of Zhejiang Chinese Medical University, National Clinical Research Base of Traditional Chinese Medicine, Hangzhou, Zhejiang 310006, P.R. China.
Department of Internal Medicine, Central Hospital of Jinhua Affiliated to Zhejiang University, Jinhua, Zhejiang 321001, P.R. China.
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.


Iron overload is commonly encountered during the course of aplastic anemia (AA), but no composite animal model has been developed yet, which hinders drug research. In the present study, the optimal dosage and duration of intraperitoneal iron dextran injection for the development of an iron overload model in mice were explored. A composite model of AA was successfully established on the principle of immune-mediated bone marrow failure. Liver volume, peripheral hemogram, bone marrow pathology, serum iron, serum ferritin, pathological iron deposition in multiple organs (liver, bone marrow, spleen), liver hepcidin, and bone morphogenetic protein 6 (BMP6), SMAD family member 4 (SMAD4) and transferrin receptor 2 (TfR2) mRNA expression levels were compared among the normal control, AA, iron overload and composite model groups to validate the composite model, and explore the pathogenesis and features of iron overload in this model. The results indicated marked increases in iron deposits, with significantly increased liver/body weight ratios as well as serum iron and ferritin in the iron overload and composite model groups as compared with the normal control and AA groups (P<0.05). There were marked abnormalities in iron regulation gene expression between the AA and composite model groups, as seen by the significant decrease of hepcidin expression in the liver (P<0.01) that paralleled the changes in BMP6, SMAD4, and TfR2. In summary, a composite mouse model with iron overload and AA was successfully established, and AA was indicated to possibly have a critical role in abnormal iron metabolism, which promoted the development of iron deposits.


animal model; aplastic anemia; iron overload; mouse

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