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首页> 外文期刊>Development >The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1.
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The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1.

机译：Chianti斑马鱼突变体为转铁蛋白受体1的红系特异性破坏提供了模型。

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摘要

Iron is a crucial metal for normal development, being required for the production of heme, which is incorporated into cytochromes and hemoglobin. The zebrafish chianti (cia) mutant manifests a hypochromic, microcytic anemia after the onset of embryonic circulation, indicative of a perturbation in red blood cell hemoglobin production. We show that cia encodes tfr1a, which is specifically expressed in the developing blood and requisite only for iron uptake in erythroid precursors. In the process of isolating zebrafish tfr1, we discovered two tfr1-like genes (tfr1a and tfr1b) and a single tfr2 ortholog. Abrogation of tfr1b function using antisense morpholinos revealed that this paralog was dispensable for hemoglobin production in red cells. tfr1b morphants exhibited growth retardation and brain necrosis, similar to the central nervous system defects observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non-erythroid tissues for iron acquisition. Overexpression of mouse Tfr1, mouse Tfr2, and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing that each of these transferrin receptors are capable of supporting iron uptake for hemoglobin production in vivo. Taken together, these data show that zebrafish tfr1a and tfr1b share biochemical function but have restricted domains of tissue expression, and establish a genetic model to study the specific function of Tfr1 in erythroid cells.
机译：铁是正常发育的关键金属，是血红素产生所必需的，血红素被掺入细胞色素和血红蛋白中。斑马鱼chianti（cia）突变体在胚胎循环开始后表现为低色素性，小细胞性贫血，表明红细胞血红蛋白产生受到干扰。我们显示，cia编码tfr1a，在发育中的血液中特别表达，并且仅是类红素前体中铁摄取的必需条件。在分离斑马鱼tfr1的过程中，我们发现了两个类似tfr1的基因（tfr1a和tfr1b）和一个tfr2直系同源物。使用反义吗啉代酶废除tfr1b功能表明该旁系同源物对于红细胞中血红蛋白的产生是可有可无的。 tfr1b morphant表现出生长迟缓和脑坏死，类似于在Tfr1 null小鼠中观察到的中枢神经系统缺陷，表明tfr1b可能被非红系组织用来获取铁。小鼠Tfr1，小鼠Tfr2和斑马鱼tfr1b的过表达部分挽救了cia胚胎中的低色素血症，从而确定了这些转铁蛋白受体中的每一个都能够支持铁的摄取，从而在体内产生血红蛋白。综上所述，这些数据表明斑马鱼tfr1a和tfr1b共享生化功能，但组织表达域受到限制，并建立了遗传模型来研究Tfr1在类红细胞中的特定功能。

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