Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL/6J mice. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Molenhuis, Remco; Bruining, Hilgo; Remmelink, Esther; de Visser, Leonie; Loos, Maarten; Burbach, J.; Kas, Martien
• Is Part Of: Journal of neurodevelopmental disorders. Volume 8:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: CNTN4 -- Autism spectrum disorder -- 3p deletion syndrome -- Developmental trajectories -- Mouse model -- Behavior -- Reversal learning -- Negative findings -- Hyperreactivity -- Schizophrenia; Developmental neurobiology -- Periodicals; Neurosciences -- Periodicals; Nervous system -- Diseases -- Periodicals; 618.928
• DOI: 10.1186/s11689-016-9140-2
• Languages: English
• ISSNs: 1866-1947

Abstract

Abstract Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence ofCNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption ofcontactin 4 (Cntn4 ) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages. Methods C57BL/6J mice with heterozygous and homozygous disruption ofCntn4 were studied through an extensive, partially longitudinal, test battery at various developmental stages, including various paradigms testing social and restricted repetitive behaviors. Results Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged inCntn4 -deficient versus wild-type mice. The impact ofCntn4 -deficiency was found to be limited to increased startle responsiveness following auditory stimuli of different high amplitudes in heterozygous and homozygousCntn4 -deficient mice and enhanced acquisition in a spatial learning task in homozygous mice. Conclusions Disruption ofCntn4 in the C57BL/6J background does not affect specific autism-related phenotypes in developing or adult mice but causes subtle non-disorder specific changes in sensory behavioral responses and cognitive performance.