期刊
NEURON
卷 89, 期 1, 页码 147-162出版社
CELL PRESS
DOI: 10.1016/j.neuron.2015.11.023
关键词
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资金
- Simons Center for the Social Brain at MIT and the Stanley Center for Psychiatric Research at Broad Institute
- National Institute of Mental Health [5R01MH097104]
- Poitras Center for Affective Disorders Research at MIT
- Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard
- Nancy Lurie Marks Family Foundation
- Simons Foundation Autism Research Initiative (SFARI)
- Simons Center for the Social Brain at MIT
- Shenzhen Overseas Innovation Team [KQTD20140630180249366]
- Stanley Center for Psychiatric Research at the Broad Institute of MIT
- Portuguese Foundation for Science and Technology [SFRH/BD/33894/2009]
- Autism Science Foundation
- Research Grant Council of Hong Kong [AoE/M09/12]
- Stanley Center for Psychiatric Research at Broad Institute of MIT
- Harvard and NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation
- Leonardo Kolleg
- Dr. Ernst und Anita Bauer-Stiftung
- Henry E. Singleton Fellowship
- NIMH through a NIH Director's Pioneer Award [DP1-MH100706]
- NINDS through a NIH Trans formative R01 grant [R01-NS 07312401]
- NSF Waterman Award
- Fundação para a Ciência e a Tecnologia [SFRH/BD/33894/2009] Funding Source: FCT
Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutation manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients.
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