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首页> 外文期刊>American Journal of Physiology >A mouse model provides evidence that genetic background modulates anemia and liver injury in erythropoietic protoporphyria.
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A mouse model provides evidence that genetic background modulates anemia and liver injury in erythropoietic protoporphyria.

机译：小鼠模型提供了证据，证明遗传背景可调节促红细胞生成性原卟啉症中的贫血和肝损伤。

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Erythropoietic protoporphyria is an inherited disorder of heme biosynthesis caused by partial ferrochelatase deficiency, resulting in protoporphyrin (PP) overproduction by erythrocytes. In humans, it is responsible for painful skin photosensitivity and, occasionally, liver failure due to accumulation of PP in the liver. The ferrochelatase deficiency mouse mutation is the best animal model available for human erythropoietic protoporphyria. The original description, based on mice with a BALB/cByJCrl genetic background, reported a disease resembling the severe form of the human disease, with anemia, jaundice, and liver failure. Using congenic strains, we investigated the effect of genetic background on the severity of the phenotype. Compared with BALB/cByJCrl, C57BL/6JCrl mice developed moderate but increasing anemia and intense liver accumulation of PP with severe hepatocyte damage and loss. Bile excretory function was not affected, and bilirubin remained low. Despite the highest PP concentration in erythrocytes, anemia was mild and there were few PP deposits in the liver in SJL/JOrlCrl homozygotes. Discriminant analysis using six hematologic and biochemical parameters showed that homozygotes of the three genetic backgrounds could be clustered in three well-separated groups. These three congenic strains provide strong evidence for independent genetic control of bone marrow contribution of PP overproduction to development of liver disease and biliary PP excretion. They provide a tool to investigate the physiological mechanisms involved in these phenotypic differences and to identify modifying genes.
机译：促红细胞生成原卟啉是由部分铁螯合酶缺乏症引起的血红素生物合成的遗传性疾病，导致原卟啉（PP）被红细胞过度生产。在人类中，它是造成皮肤疼痛性光敏性的原因，有时是由于肝脏中PP的积累而引起的肝功能衰竭。铁螯合酶缺乏症小鼠突变是可用于人类促红细胞性原卟啉症的最佳动物模型。最初的描述基于具有BALB / cByJCrl遗传背景的小鼠，报道了一种类似于人类疾病的严重形式的疾病，包括贫血，黄疸和肝功能衰竭。使用同系菌株，我们调查了遗传背景对表型严重性的影响。与BALB / cByJCrl相比，C57BL / 6JCrl小鼠出现中度但逐渐增加的贫血和严重的PP肝蓄积，严重肝细胞受损和丢失。胆汁排泄功能不受影响，胆红素仍然很低。尽管红细胞中的PP浓度最高，但贫血是轻度的，SJL / JOrlCrl纯合子的肝脏中PP沉积很少。使用六个血液学和生化参数的判别分析显示，三个遗传背景的纯合子可以聚集在三个分隔良好的组中。这三个同系菌株为PP过量生产对肝脏疾病和胆汁PP排泄的发展的骨髓贡献的独立遗传控制提供了有力证据。它们提供了一种工具来研究涉及这些表型差异的生理机制并鉴定修饰基因。

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