Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome

Details

Serval ID
serval:BIB_01290DE77F5E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome
Journal
Human Molecular Genetics
Author(s)
Chrast  R., Scott  H. S., Madani  R., Huber  L., Wolfer  D. P., Prinz  M., Aguzzi  A., Lipp  H. P., Antonarakis  S. E.
ISSN
0964-6906 (Print)
Publication state
Published
Issued date
07/2000
Volume
9
Number
12
Pages
1853-64
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul 22
Abstract
The Drosophila single-minded (sim) transcription factor, is a master regulator of fruitfly neurogenesis. Recently, we have cloned and mapped a human homolog of sim, SIM2, to chromosome 21 in the so-called 'Down syndrome chromosomal region'. Three copies of SIM2 may contribute to some Down syndrome (DS) phenotypes because of the mapping position function as transcriptional repressor, temporal and spatial expression pattern of mouse Sim2, and the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis. In order to validate this hypothesis in vivo, we have created the first bacterial artificial chromosome transgenic mice overexpressing a gene possibly involved in DS with only one or two additional copies of mouse Sim2. The transgene was shown to be expressed in the same spatial pattern as the endogenous gene. The mice develop normally, are fertile and do not show detectable histopathological abnormalities. However, detailed analysis of their behavior revealed anxiety-related/reduced exploratory behaviour and sensitivity to pain, phenotypes similar to those also present in other partial trisomy 16 mouse models of DS. Our data therefore suggest that overexpression of SIM2 contributes to some of the complex DS phenotypes.
Keywords
Animals Basic Helix-Loop-Helix Transcription Factors Behavior, Animal Chromosomes, Bacterial DNA-Binding Proteins/genetics/*physiology Disease Models, Animal Down Syndrome/*etiology Drosophila Proteins Female Gene Dosage Gene Expression Profiling Humans Mice Mice, Inbred C57BL Mice, Transgenic Motor Activity Nuclear Proteins/genetics/*physiology Pain Measurement Phenotype Social Behavior Stress Trisomy
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:12
Last modification date
08/05/2019 13:40
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