Genetic contribution to language-related preclinical biomarkers of autism

  • Awarded: 2013
  • Award Type: Research
  • Award #: 275555

Children with autism have been shown to display an increased latency of auditory processing, as measured by the electroencephalography (EEG) response to a sound as well as differences in brain activity at rest1.

Similarly, well-accepted mouse models of autism, including both mice with prenatal exposure to valproic acid and those with alterations in NMDA receptor signaling, reflect these alterations in mouse-equivalent measures1-6. The current study assessed the degree to which mice with a deletion of the 16p11.2 chromosomal region also reflect the autism-like alterations in auditory EEG.

Steven Siegel and his group’s preliminary data indicate that the current cohort of mice with 16p11.2 deletion have normal hearing. Thus far, data do not indicate that these mice exhibit the type of increased latency of auditory cortex activation described in people with autism and in mouse models of idiopathic autism. However, preliminary data do indicate that there are sex-specific alterations in the pattern of brain activation following sensory stimulation. Specifically, female deletion mice exhibit lower, and male deletion mice exhibit higher orienting to externally generated events (for example, a sound).

These sexually dimorphic findings in 16p11.2 deletion mice suggest that the current model system is potentially sensitive to factors that contribute to the differential incidence and expression of autism among boys and girls. As such, it may be useful in assessing sexually specific effects of new therapeutic approaches.

 

References

  1.  Gandal M.J. et al. Biol. Psychiatry 68, 1100-1106 (2010) PubMed
  2. Billingslea E.N. et al. Neuropsychopharmacology 39, 1603-1613 (2014) PubMed
  3. Gandal M.J. et al. Genes Brain Behav. 11, 740-750 (2012) PubMed
  4. Mehta M.V. et al. PLoS One 6, e26077 (2011) PubMed
  5. Saunders J.A. et al. Behav. Brain Res. 234, 233-237 (2012) PubMed
  6. Saunders J.A. et al. Autism Res. 6, 69-77 (2013) PubMed
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