Social approach in genetically engineered mouse lines relevant to autism
| Autor: | Jean M. Lauder, Randal J. Nonneman, Jacqueline N. Crawley, Terry Magnuson, A. J. D'Ercole, A. W. Grossman, Sheryl S. Moy, Jessica J. Nadler, Dennis L. Murphy, Nancy B. Young |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Genetically modified mouse Oxidoreductases Acting on CH-CH Group Donors Nerve Tissue Proteins Anxiety Motor Activity Social identity approach Article Fragile X Mental Retardation Protein Mice Behavioral Neuroscience Neurodevelopmental disorder Pregnancy Genetics medicine Animals Autistic Disorder Insulin-Like Growth Factor I Social Behavior Postural Balance Serotonin transporter Homeodomain Proteins Mice Knockout Serotonin Plasma Membrane Transport Proteins Sex Characteristics Behavior Animal biology medicine.disease FMR1 Social relation Mice Inbred C57BL Smell Neurology Endophenotype Exploratory Behavior biology.protein Autism Female Food Deprivation Genetic Engineering Psychology |
| Zdroj: | Genes, Brain and Behavior. 8:129-142 |
| ISSN: | 1601-183X 1601-1848 |
| DOI: | 10.1111/j.1601-183x.2008.00452.x |
| Popis: | Profound impairment in social interaction is a core symptom of autism, a severe neurodevelopmental disorder. Deficits can include a lack of interest in social contact and low levels of approach and proximity to other children. In this study, a three-chambered choice task was used to evaluate sociability and social novelty preference in five lines of mice with mutations in genes implicated in autism spectrum disorders. Fmr1tm1Cgr/Y (Fmr1−/y) mice represent a model for fragile X, a mental retardation syndrome that is partially co-morbid with autism. We tested Fmr1−/y mice on two genetic backgrounds, C57BL/6J and FVB/N-129/OlaHsd (FVB/129). Targeted disruption of Fmr1 resulted in low sociability on one measure, but only when the mutation was expressed on FVB/129. Autism has been associated with altered serotonin levels and polymorphisms in SLC6A4 (SERT), the serotonin-transporter gene. Male mice with targeted disruption of Slc6a4 displayed significantly less sociability than wildtype controls. Mice with conditional overexpression of Igf-1 (Insulin-like growth factor-1) offered a model for brain overgrowth associated with autism. Igf-1 transgenic mice engaged in levels of social approach similar to wildtype controls. Targeted disruption in other genes of interest, En2 (Engrailed 2) and Dhcr7, was carried on genetic backgrounds that demonstrated low levels of exploration in the choice task, precluding meaningful interpretations of social behavior scores. Overall, results show that loss of Fmr1 or Slc6a4 gene function can lead to deficits in sociability. Findings from the fragile X-model suggest that the FVB/129 background confers enhanced susceptibility to consequences of Fmr1 mutation on social approach. |
| Databáze: | OpenAIRE |
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