Behavioral evaluation of a novel autism mouse model

  • Awarded: 2014
  • Award Type: Explorer
  • Award #: 286567

Many young children with autism show brain overgrowth soon after birth, suggesting a very early, possibly prenatal origin of autism-linked neuropathological features. Recent findings of substantially increased neuron numbers in the prefrontal cortex of children with autism1 considerably strengthened this notion, as neurogenesis in humans occurs during embryonic and fetal development.

Konstantinos Zarbalis and his colleagues at the Shriners Hospital for Children – Northern California and the University of California, Davis generated two mouse lines that carry mutations in the WDFY3 gene, which also mutates in some children with autism. Analogous to a subset of young children with autism, WDFY3-deficient mice show abnormal cerebral overgrowth in a stereotypical gradient.

The neurodevelopmental analysis of WDFY3 mutant mice reveals an important role of WDFY3 in regulating the division of neural progenitors. Loss of WDFY3 leads to increased proliferation of neural progenitors, which eventually leads to more neurons and larger brains.

Zarbalis and his team, together with Jacqueline Crawley of the University of California, Davis MIND Institute, aim to determine the extent to which carriers of WDFY3 mutant alleles display behavioral phenotypes relevant to diagnostic and associated symptoms of autism. They hope to further explore the possibility that defects in the proliferative behavior of neural progenitors play a fundamental role in the development of autism.



1.Courchesne E. et al. JAMA 306, 2001-2010 (2011) PubMed
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