Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis.
Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis.
复制标题
3型血色素沉着症小鼠模型的红细胞生成发生改变
DOI：
10.1155/2017/2408941
复制
发表时间：
2017
影响因子：
--
通讯作者：
Roetto A
中科院分区：
文献类型：
--
作者：
Pellegrino RM;Riondato F;Ferbo L;Boero M;Palmieri A;Osella L;Pollicino P;Miniscalco B;Saglio G;Roetto A
3型血色病（HFE 3）是一种罕见的遗传性铁超负荷疾病，最终导致器官功能受损。HFE 3由转铁蛋白受体2（TFR2）基因突变引起，该基因编码两种主要亚型（Tfr 2 α和Tfr 2 β）。Tfr 2 α是铁抑制剂hepcidin的肝脏调节剂之一。Tfr2β是网状内皮细胞中参与调节铁水平的蛋白质的细胞内同种型。最近已经证明Tfr 2也参与红细胞生成。本研究旨在通过评价两种Tfr 2小鼠模型的红细胞生成来进一步研究Tfr 2的红细胞生成作用，其中一种或两种Tfr 2亚型已被选择性沉默（Tfr 2 KI和Tfr 2 KO）。在14日龄和10周龄小鼠的骨髓和脾脏中进行评价，以评估年轻动物与成年动物的红细胞生成。缺乏Tfr 2 α导致大红细胞症伴网织红细胞数量减少和血红蛋白值升高，以及预期成人BM红细胞生成和脾红细胞生成增加。另一方面，缺乏Tfr 2 β（Tfr 2 KI小鼠）导致脾红细胞生成增加和不成熟。总之，这些数据证实了Tfr 2 α在调节红细胞生成中的作用和Tfr 2 β在促进红细胞生成的铁可用性中的作用。
Type 3 haemochromatosis (HFE3) is a rare genetic iron overload disease which ultimately lead to compromised organs functioning. HFE3 is caused by mutations in transferrin receptor 2 (TFR2) gene that codes for two main isoforms (Tfr2α and Tfr2β). Tfr2α is one of the hepatic regulators of iron inhibitor hepcidin. Tfr2β is an intracellular isoform of the protein involved in the regulation of iron levels in reticuloendothelial cells. It has been recently demonstrated that Tfr2 is also involved in erythropoiesis. This study aims to further investigate Tfr2 erythropoietic role by evaluating the erythropoiesis of two Tfr2 murine models wherein either one or both of Tfr2 isoforms have been selectively silenced (Tfr2 KI and Tfr2 KO). The evaluations were performed in bone marrow and spleen, in 14 days' and 10 weeks' old mice, to assess erythropoiesis in young versus adult animals. The lack of Tfr2α leads to macrocytosis with low reticulocyte number and increased hemoglobin values, together with an anticipation of adult BM erythropoiesis and an increased splenic erythropoiesis. On the other hand, lack of Tfr2β (Tfr2 KI mice) causes an increased and immature splenic erythropoiesis. Taken together, these data confirm the role of Tfr2α in modulation of erythropoiesis and of Tfr2β in favoring iron availability for erythropoiesis.