The effect of background strain on the behavioral phenotypes of the MDGA2+/- mouse model of autism spectrum disorder

Genes Brain Behav. 2021 Mar;20(3):e12696. doi: 10.1111/gbb.12696. Epub 2020 Sep 11.

Abstract

The membrane-associated mucin (MAM) domain containing glycosylphosphatidylinositol anchor 2 protein single knock-out mice (MDGA2+/- ) are models of ASD. We examined the behavioral phenotypes of male and female MDGA2+/- and wildtype mice on C57BL6/NJ and C57BL6/N backgrounds at 2 months of age and measured MDGA2, neuroligin 1 and neuroligin 2 levels at 7 months. Mice on the C57BL6/NJ background performed better than those on the C57BL6/N background in visual ability and in learning and memory performance in the Morris water maze and differed in measures of motor behavior and anxiety. Mice with the MDGA2+/- genotype differed from WT mice in motor, social and repetitive behavior and anxiety, but most of these effects involved interactions between MDGA2+/- genotype and background strain. The background strain also influenced MDGA2 levels and NLGN2 association in MDGA2+/- mice. Our findings emphasize the importance of the background strain used in studies of genetically modified mice.

Keywords: autism; background strain; mouse model; sex differences; social interaction; stereotypy; synaptic proteins; vision.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics*
  • Female
  • GPI-Linked Proteins / genetics*
  • Genetic Background*
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • Neural Cell Adhesion Molecules / genetics*
  • Phenotype*
  • Social Behavior

Substances

  • GPI-Linked Proteins
  • MDGA2 protein, mouse
  • Neural Cell Adhesion Molecules