Mouse models of the human porphyrias have proven useful for investigations of disease pathogenesis and to facilitate the development of new therapeutic approaches. To date, mouse models have been generated for all major porphyrias, with the exception of X-linked protoporphyria (XLP) and the ultra rare 5-aminolevulinic acid dehydratase deficient porphyria (ADP). Mouse models have been generated for the three autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). The AIP mice, in particular, provide a useful investigative model as they have been shown to have acute biochemical attacks when induced with the prototypic porphyrinogenic drug, phenobarbital. In addition to providing important insights into the disease pathogenesis of the neurological impairment in AIP, these mice have been valuable for preclinical evaluation of liver-targeted gene therapy and RNAi-mediated approaches. Mice with severe HMBS deficiency, which clinically and biochemically mimic the early-onset homozygous dominant AIP (HD-AIP) patients, have been generated and were used to elucidate the striking phenotypic differences between AIP and HD-AIP. Mice modeling the hepatocutaneous porphyria, porphyria cutanea tarda (PCT), made possible the identification of the iron-dependent inhibitory mechanism of uroporphyrinogen decarboxylase (UROD) that leads to symptomatic PCT. Mouse models for the two autosomal recessive erythropoietic porphyrias, congenital erythropoietic porphyria (CEP) and erythropoeitic protoporphyria (EPP), recapitulate many of the clinical and biochemical features of the severe human diseases and have been particularly useful for evaluation of bone marrow transplantation and hematopoietic stem cell (HSC)-based gene therapy approaches. The EPP mice have also provided valuable insights into the underlying pathogenesis of EPP-induced liver damage and anemia.

中文翻译：

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人类卟啉症的鼠模型：有助于理解疾病的发病机理和新疗法的发展。

事实证明，人类卟啉症的小鼠模型可用于研究疾病发病机理并促进新治疗方法的开发。迄今为止，已经为所有主要的卟啉症建立了小鼠模型，除了X连锁原卟啉症（XLP）和极少见的5-氨基乙酰丙酸脱水酶缺陷性卟啉症（ADP）。已为三种常染色体显性急性肝卟啉症，急性间歇性卟啉症（AIP），遗传性结肠卟啉症（HCP）和杂色卟啉症（VP）生成了小鼠模型。特别是，AIP小鼠提供了有用的研究模型，因为当它们被原型卟啉原性药物苯巴比妥诱导时，具有急性生化攻击。除了提供有关AIP中神经功能障碍的疾病发病机理的重要见解之外，这些小鼠对于肝靶向基因治疗和RNAi介导的方法的临床前评估也很有价值。已产生严重HMBS缺乏症的小鼠，该小鼠在临床和生物化学上模仿了早期发作的纯合子优势AIP（HD-AIP）患者，并用于阐明AIP和HD-AIP之间显着的表型差异。小鼠对肝皮卟啉症，皮肤卟啉卟啉（PCT）进行建模，使得鉴定导致症状性PCT的尿卟啉原脱羧酶（UROD）的铁依赖性抑制机制成为可能。两种常染色体隐性遗传性红斑卟啉症，先天性促红细胞性卟啉症（CEP）和促红细胞生成性原卟啉症（EPP）的小鼠模型，概述了严重人类疾病的许多临床和生化特征，对于评估骨髓移植和基于造血干细胞（HSC）的基因治疗方法特别有用。EPP小鼠还为EPP引起的肝损伤和贫血的潜在发病机理提供了有价值的见解。