Resistance to change and vulnerability to stress: autistic-like features of GAP43-deficient mice

Genes Brain Behav. 2010 Nov;9(8):985-96. doi: 10.1111/j.1601-183X.2010.00638.x.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Psychological / physiology*
  • Analysis of Variance
  • Animals
  • Anxiety / complications
  • Anxiety / genetics
  • Autistic Disorder / genetics*
  • Autistic Disorder / psychology
  • Disease Models, Animal
  • Female
  • GAP-43 Protein / genetics*
  • Genetic Predisposition to Disease
  • Heterozygote
  • Male
  • Maze Learning / physiology
  • Mice
  • Social Behavior*
  • Statistics, Nonparametric
  • Stress, Psychological / complications
  • Stress, Psychological / genetics*


  • GAP-43 Protein