Human Molecular Genetics Advance Access originally published online on May 10, 2008
Human Molecular Genetics 2008 17(16):2486-2495; doi:10.1093/hmg/ddn148
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Abnormal social behaviors and altered gene expression rates in a mouse model for Potocki-Lupski syndrome
1 Centro de Estudios Científicos, CECS, Valdivia, Chile 2 Universidad Austral de Chile, Valdivia, Chile 3 The Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland 4 Department of Molecular and Human Genetics 5 Department of Pediatrics, Baylor College of Medicine 6 Texas Children’s Hospital, Houston, TX, USA
* To whom correspondence should be addressed at: Avda. Prat 514, 5110246 Valdivia, Chile. Tel: +56 63234514; Fax: +56 63234517; Email: kwalz{at}cecs.cl
Received February 27, 2008; Accepted May 7, 2008
The Potocki-Lupski syndrome (PTLS) is associated with a microduplication of 17p11.2. Clinical features include multiple congenital and neurobehavioral abnormalities and autistic features. We have generated a PTLS mouse model, Dp(11)17/+, that recapitulates some of the physical and neurobehavioral phenotypes present in patients. Here, we investigated the social behavior and gene expression pattern of this mouse model in a pure C57BL/6-Tyrc-Brd genetic background. Dp(11)17/+ male mice displayed normal home-cage behavior but increased anxiety and increased dominant behavior in specific tests. A subtle impairment in the preference for a social target versus an inanimate target and abnormal preference for social novelty (the preference to explore an unfamiliar mouse versus a familiar one) was also observed. Our results indicate that these animals could provide a valuable model to identify the specific gene(s) that confer abnormal social behaviors and that map within this delimited genomic deletion interval. In a first attempt to identify candidate genes and for elucidating the mechanisms of regulation of these important phenotypes, we directly assessed the relative transcription of genes within and around this genomic interval. In this mouse model, we found that candidates genes include not only most of the duplicated genes, but also normal-copy genes that flank the engineered interval; both categories of genes showed altered expression levels in the hippocampus of Dp(11)17/+ mice.
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