A Genetic Model of Perinatal Iron Deficiency

围产期缺铁的遗传模型

基本信息

批准号：
6998625
负责人：
Erik Sean Carlson
金额：
$ 3.28万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-08 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6998625
关键词：
behavior test brain morphology developmental neurobiology electrophysiology gene deletion mutation gene expression genetic models genetically modified animals hippocampus immunocytochemistry iron disorder iron metabolism laboratory mouse membrane transport proteins neurogenetics neuropathology neuropsychology predoctoral investigator

项目摘要

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.

描述（由申请人提供）：该项目的目标是评估区域和时间特异性缺铁（ID）对小鼠条件性敲除模型中发育中的海马体的结构和行为影响。海马体被广泛认为在包括学习和记忆在内的多种认知功能中具有至关重要的作用。不幸的是，在围产期，海马体比其他大脑区域更容易受到许多伤害，例如智力障碍（Erickson et al, 1997）。 ID 是世界上最普遍的微量营养素缺乏症，仅在美国每年就有约 250,000 名新生儿受到影响。围产期 ID 导致的认知缺陷持续到成年期（Lozoff 等，2000）。利用铁的饮食限制（这是与美国人类中所见的智力障碍的病因不同）的动物研究显示了结构、生化和认知障碍，但未能澄清对海马体的影响是否确实是由于智力障碍造成的。构成海马体的细胞，或由于与饮食 ID 相关的其他病理生理状态（贫血、缺氧）而发生。我们正在使用铁转运蛋白 (DMT1) 的条件 KO 模型，并将检查其对与学习和记忆相关的结构和行为表型的影响。