Mild impairment of learning and memory in mice overexpressing the mSim2 gene located on chromosome 16: an animal model of Down's syndrome.
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.
Ema
M
M
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan,
Ikegami
S
S
Hosoya
T
T
Mimura
J
J
Ohtani
H
H
Nakao
K
K
Inokuchi
K
K
Katsuki
M
M
Fujii-Kuriyama
Y
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001522:Behavior, Animal / Q000502:physiology; D002875:Chromosomes / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D003213:Conditioning, Psychological / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics; D029721:Drosophila Proteins; D005239:Fear; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics / Q000503:physiopathology*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013550:Swimming; D014018:Tissue Distribution
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C417032:SIM2 protein, human; C089449:sim protein, Drosophila