title: Resistance to change and vulnerability to stress: autistic-like features of GAP43-deficient mice.
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.
authors: Department of Cell & Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA. zaccarik@upstate.edu
authors: K J
authors: KJ
authors: Zaccaria
authors: D C
authors: DC
authors: Lagace
authors: A J
authors: AJ
authors: Eisch
authors: J S
authors: JS
authors: McCasland
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D012919:Social Behavior; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics*
chemical_list: D019922:GAP-43 Protein