title: Are Sema5a mutant mice a good model of autism? A behavioral analysis of sensory systems, emotionality and cognition.
abstract: Semaphorin 5A (Sema5A) expression is reduced in the brain of individuals with autism, thus mice with reduced Sema5A levels may serve as a model of this neurodevelopmental disorder. We tested male and female Sema5a knockout mice (B6.129P2SEMA5A(<)™(1DGEN>)/J) and C57BL/6J controls for emotionality, visual ability, prepulse inhibition, motor learning and cognition. Overall, there were only two genotype differences in emotionality: Sema5a mutant mice had more stretch-attend postures in the elevated plus-maze and more defecations in the open field. All mice could see, but Sema5a mice had better visual ability than C57BL/6J mice. There were no genotype differences in sensory-motor gating. Sema5a mice showed higher levels of activity in the elevated plus-maze and light/dark transition box, and there were sex by genotype differences in the Rotarod, suggesting a sex difference in balance and coordination differentially affected by Sema5a. There were no genotype effects on cognition: Sema5a mice did not differ from C57BL/6J in the Morris water maze, set-shifting or cued and contextual fear conditioning. In the social recognition test, all mice preferred social stimuli, but there was no preference for social novelty, thus the Sema5A mice do not have a deficit in social behavior. Overall, there were a number of sex differences, with females showing greater activity and males performing better in tests of spatial learning and memory, but no deficits in the behavior of Sema5A mice. We conclude that the Sema5a mice do not meet the behavioral criteria for a mouse model of autism.
authors.affiliation: Psychology Department, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Rhian K
authors.initials: RK
authors.lastname: Gunn
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Huentelman
authors.forename: Richard E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000150:complications* / Q000235:genetics*; D001526:Behavioral Symptoms / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology*; D003213:Conditioning, Psychological / Q000502:physiology; D003623:Dark Adaptation / Q000235:genetics; D004192:Discrimination, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear; D005260:Female; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D045442:Rotarod Performance Test; D039961:Semaphorins; D012678:Sensation Disorders / Q000209:etiology*; D055139:Sensory Gating / Q000235:genetics; D012737:Sex Factors; D012919:Social Behavior; D014796:Visual Perception / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C103619:Sema5A protein, mouse; D039961:Semaphorins