Generation of malignant tumor model by heme synthesis failure using mice with Abcb10 deficient

为了研究Abcb10缺乏对PPIX积聚和肿瘤细胞恶性潜能的影响，我们试图从DEN暴露的Abcb10-/-小鼠建立同种异体肿瘤移植-转移模型。我们从Abcb10-/-小鼠的肝脏肿瘤中提取了几个细胞，但没有获得任何具有自发转移潜能的肿瘤细胞。我们详细地探索了Abcb10的生理作用与肿瘤发生的相关性。Abcb10缺乏导致血红素生物合成缺陷，但不影响FECH的稳定性。Abcb10-/-造血细胞的电子显微镜图像显示线粒体有明显的铁沉积。Abcb10F/-；Mx1-Cre小鼠在造血细胞中特异性缺失了Abcb10，在网织红细胞中表现出PPIX积聚和成熟停滞。这些结果表明Abcb10在血红素生物合成中起关键作用，并为红细胞原始卟啉和铁粒母细胞性贫血的发病机制提供了新的见解。

To investigate how Abcb10 deficiency affect to the accumulation of PPIX and malignant potential of tumor cells, we tried to generate allogeneic tumor transplantation-metastasis models from DEN exposed Abcb10-/-mice. We picked up several cells from liver tumors of Abcb10-/-mice, however could not obtain any tumor cells that acquired spontaneous metastatic potential.We explored in detail the relevance of the physiological role of Abcb10 to the tumorigenesis. Abcb10 deficiency resulted in a defect of heme biosynthesis but did not affect to the stability of Fech. Electron microscopy images of Abcb10-/- hematopoietic cells showed marked iron deposits at the mitochondria. Abcb10F/-; Mx1-Cre mice, with the specific deletion of Abcb10 in hematopoietic cells, showed PPIX accumulation and maturation arrest in reticulocytes.These results suggest a critical role for Abcb10 in heme biosynthesis and provide new insights into the pathogenesis of erythropoietic protoporphyria and sideroblastic anemia.