Reduced exploration, increased anxiety, and altered social behavior: Autistic-like features of euchromatin histone methyltransferase 1 heterozygous knockout mice

Behav Brain Res. 2010 Mar 17;208(1):47-55. doi: 10.1016/j.bbr.2009.11.008. Epub 2009 Nov 5.

Abstract

The 9q34.3 subtelomeric deletion syndrome is a newly defined mental retardation syndrome, caused by haplo-insufficiency of the euchromatin histone methyltransferase 1 (EHMT1) gene. Patients also have childhood hypotonia, facial dysmorphisms, delay in reaching developmental milestones, and behavioral problems like aggressive outbursts, hypoactivity, or autistic-like features. Male and female heterozygous Ehmt1 knockout mice (Ehmt1(+/-), aged 1-20 months, kept on a C57BL/6J background), were used to investigate whether they mimic the patients behavioral characteristics by comparing their behavior to wildtype littermates. The Ehmt1(+/-) mice revealed reduced activity and exploration, with increased anxiety compared to wildtype mice when exposed to novel environments in the open field, object exploration, marble burying, light-dark box, mirrored chamber and T-maze tests. They also demonstrated diminished social play when encountering a mouse from a different litter, and a delayed or absent response to social novelty when exposed to a stranger mouse. However, no differences in phenotyper home cage locomotor activity or rotarod motor function were observed between Ehmt1(+/-) and wildtype mice. Together, these results indicate that the hypoactivity and the autistic-like features of 9q34.3 subtelomeric deletion syndrome patients are recapitulated in this Ehmt1(+/-) mouse model, and that the hypoactivity is apparently not caused by any motor dysfunction. Together, these observations make it plausible that the Ehmt1(+/-) mouse is a faithful mammalian model for the autistic-like behavioral features of patients with the 9q34.3 subtelomeric deletion syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Ocular / physiology
  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Anxiety / etiology*
  • Autistic Disorder / complications*
  • Autistic Disorder / genetics*
  • Body Weight / genetics
  • Disease Models, Animal
  • Euchromatin / genetics
  • Exploratory Behavior / physiology*
  • Female
  • Genotype
  • Grooming / physiology
  • Histone-Lysine N-Methyltransferase / deficiency*
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics
  • Sex Factors
  • Social Behavior*

Substances

  • Euchromatin
  • Histone-Lysine N-Methyltransferase