Abstract
There is an urgent need for animal models of autism spectrum disorder (ASD) to understand the underlying pathology and facilitate development and testing of new treatments. The synaptic growth-associated protein-43 (GAP43) has recently been identified as an autism candidate gene of interest. Our previous studies show many brain abnormalities in mice lacking one allele for GAP43 [GAP43 (+/-)] that are consistent with the disordered connectivity theory of ASD. Thus, we hypothesized that GAP43 (+/-) mice would show at least some autistic-like behaviors. We found that GAP43 (+/-) mice, relative to wild-type (+/+) littermates, displayed resistance to change, consistent with one of the diagnostic criteria for ASD. GAP43 (+/-) mice also displayed stress-induced behavioral withdrawal and anxiety, as seen in many autistic individuals. In addition, both GAP43 (+/-) mice and (+/+) littermates showed low social approach and lack of preference for social novelty, consistent with another diagnostic criterion for ASD. This low sociability is likely because of the mixed C57BL/6J 129S3/SvImJ background. We conclude that GAP43 deficiency leads to the development of a subset of autistic-like behaviors. As these behaviors occur in a mouse that displays disordered connectivity, we propose that future anatomical and functional studies in this mouse may help uncover underlying mechanisms for these specific behaviors. Strain-specific low sociability may be advantageous in these studies, creating a more autistic-like environment for study of the GAP43-mediated deficits of resistance to change and vulnerability to stress.
Original language | English (US) |
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Pages (from-to) | 985-996 |
Number of pages | 12 |
Journal | Genes, Brain and Behavior |
Volume | 9 |
Issue number | 8 |
DOIs | |
State | Published - Nov 2010 |
Keywords
- Animal
- Anxiety behavior
- Autistic disorder
- Behavior
- Disease models
- GAP43
- Maze learning
- Mice
- Mutant strains
- Reversal learning
- Social behavior
ASJC Scopus subject areas
- Genetics
- Neurology
- Behavioral Neuroscience