Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16:: an animal model of Down's syndrome

被引:67
作者
Ema, M
Ikegami, S
Hosoya, T
Mimura, J
Ohtani, H
Nakao, K
Inokuchi, K
Katsuki, M
Fujii-Kuriyama, Y [1 ]
机构
[1] Tohoku Univ, Grad Sch Sci, Dept Chem, Sendai, Miyagi 9808578, Japan
[2] Mitsubishi Kasei Inst Life Sci, Machida, Tokyo 1948511, Japan
[3] Univ Tokyo, Inst Med Sci, Dept DNA Biol & Embryo Engn, Tokyo 1080071, Japan
[4] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 9808574, Japan
关键词
D O I
10.1093/hmg/8.8.1409
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human Sim2 is a product of one of the genes located on human chromosome 21q22 and is a homolog of Drosophila single-minded (sim) which is a critical player in midline development of the central nervous system of the fly, Since Sim2 mRNA is expressed in facial, skull, palate and vertebra primordia in human and rodent embryos, features that are associated with phenotypes of Down's syndrome (DS), its trisomic state is suspected to contribute to the symptoms of DS, Here we describe that mSim2 mRNA is expressed in hippocampus and amygdala of adult mice, and that while mice overexpressing mSim2 under the control of the beta-actin promoter are viable and fertile and have superficially normal skeletal, brain and heart structures, they exhibit a moderate defect in context-dependent fear conditioning and a mild defect in the Morris water maze test. Taken together, our data show that overdosage of Sim2 may be important for the pathogenesis of Down's syndrome, especially mental retardation.
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页码:1409 / 1415
页数:7
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