A Genetic Model of Perinatal Iron Deficiency

描述（由申请人提供）：本项目的目标是在小鼠条件性基因敲除模型中评估区域和时间特异性铁缺乏（ID）对发育中海马的结构和行为影响。海马体被广泛认为在包括学习和记忆在内的几种认知功能中具有至关重要的作用。不幸的是，在围产期，海马比其他脑区更容易受到许多损伤，如ID（Erickson等，1997）。ID是世界上最普遍的微量营养素缺乏症，仅在美国每年就影响约25万新生儿。围产期ID导致的认知缺陷持续到成年期（Lozoff et al，2000）。利用铁的饮食限制（这是与美国人类中所见的ID不同的病因学）的动物研究已经显示出结构、生物化学和认知障碍，但未能澄清对海马的影响是否确实是由于组成海马的细胞中的ID，还是由于与饮食ID一起发生的其他病理生理状态（贫血、缺氧）。我们正在使用铁转运蛋白（DMT 1）的条件KO模型，并将研究其对与学习和记忆相关的结构和行为表型的影响。

DESCRIPTION (provided by applicant): The goal of this project is to evaluate the structural and behavioral effects of region and temporally specific iron deficiency (ID) on the developing hippocampus in a mouse conditional knockout model. The hippocampus is widely recognized as having paramount importance in several cognitive functions, including learning and memory. Unfortunately, the hippocampus is more susceptible than other brain areas during the perinatal period to many insults such as ID (Erickson et al, 1997). ID is the most prevalent micronutrient deficiency in the world, and affects some 250,000 neonates each year in the USA alone. Cognitive deficits resulting from perinatal ID persist into adulthood (Lozoff et al, 2000). Animal studies utilizing dietary restriction (which is a different etiology of ID than is seen in humans in the US) of iron have shown structural, biochemical, and cognitive impairments, but fail to clarify whether the effect on the hippocampus is indeed due to ID in the cells comprising the hippocampus, or due to other pathophysiological states that occur in conjunction with dietary ID (anemia, hypoxia). We are using a conditional KO model of an iron transporter (DMT1), and will examine its effects on structural and behavioral phenotypes related to learning & memory.