Social approach in genetically engineered mouse lines relevant to autism.
Genes Brain Behav
; 8(2): 129-42, 2009 Mar.
Article
em En
| MEDLINE
| ID: mdl-19016890
ABSTRACT
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. Fmr1(tm1Cgr/Y)(Fmr1(-/y)) mice represent a model for fragile X, a mental retardation syndrome that is partially comorbid 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 wild-type 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 wild-type controls. Targeted disruption in other genes of interest, En2 (engrailed-2) and Dhcr7, was carried on genetic backgrounds that showed 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
/
Comportamento Social
/
Engenharia Genética
/
Camundongos Knockout
Tipo de estudo:
Prognostic_studies
Aspecto:
Determinantes_sociais_saude
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Genes Brain Behav
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos