Early embryonic lethality of H ferritin gene deletion in mice
Early embryonic lethality of H ferritin gene deletion in mice
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DOI：
10.1074/jbc.275.5.3021
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发表时间：
2000-02-04
影响因子：
4.8
通讯作者：
Beaumont, C
中科院分区：
文献类型：
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作者：
Ferreira, C;Bucchini, D;Beaumont, C
铁蛋白分子在控制细胞内铁的分布和长期铁库的构建中起重要作用。重组铁蛋白亚基的体外研究表明，与H亚基相关的铁氧化酶活性是铁蛋白分子摄取铁所必需的，而L亚基促进蛋白质壳内的铁核心形成。然而，植物和细菌铁蛋白只有一种类型的亚基，可能履行这两种功能。为了评估与H亚基相关的铁氧化酶活性的生物学意义，我们通过同源重组破坏了小鼠的H铁蛋白基因（Fth）。Fth（+/-）小鼠是健康的、可生育的，并且与它们的对照同窝出生的小鼠没有显著差异。然而，Fth（-/-）胚胎在发育的3.5天和9.5天之间死亡，这表明在两个铁蛋白亚基之间没有功能冗余，并且在不存在H亚基的情况下，L铁蛋白均聚物不能将铁维持在生物可利用的和无毒的形式。野生型Fth基因在9.5天胚胎中的表达模式提示了H铁蛋白基因在心脏中的重要功能。
Ferritin molecules play an important role in the control of intracellular iron distribution and in the constitution of long term iron stores. In vitro studies on recombinant ferritin subunits have shown that the ferroxidase activity associated with the H subunit is necessary for iron uptake by the ferritin molecule, whereas the L subunit facilitates iron core formation inside the protein shell. However, plant and bacterial ferritins have only a single type of subunit which probably fulfills both functions. To assess the biological significance of the ferroxidase activity associated with the H subunit, we disrupted the H ferritin gene (Fth) in mice by homologous recombination. Fth(+/-) mice are healthy, fertile, and do not differ significantly from their control littermates, However, Fth(-/-) embryos die between 3.5 and 9.5 days of development, suggesting that there is no functional redundancy between the two ferritin subunits and that, in the absence of H subunits, L ferritin homopolymers are not able to maintain iron in a bioavailable and nontoxic form. The pattern of expression of the wild type Fth gene in 9.5-day embryos is suggestive of an important function of the H ferritin gene in the heart.