Microcephaly is a hallmark of Angelman syndrome (AS), a debilitating neurodevelopmental disorder that results from loss of function of the HECT domain E3 ubiquitin ligase, UBE3A. However, until recently, the underlying causes of slowed brain growth in individuals with AS had gone unstudied, resulting in significant gaps in understanding of the pathogenesis of the disorder.
A team of scientists led by Ben Philpot at the UNC Neuroscience Center used complementary MRI-DTI, light microscopy, and electron microscopy approaches in AS model mice to show that the growth and integrity of white matter pathways are preferentially affected in the developing brain as a consequence of UBE3A loss. Deficient white matter development thus appears to largely account for the microcephaly phenotype. Philpot and colleagues also found that white matter deficits in AS mice correlate with defects in nerve conduction, which may contribute to motor dysfunction and perhaps other behavioral phenotypes commonly observed in individuals with AS. The study was published on August 2, 2017 in The Journal of Neuroscience.
Matthew Judson is a Research Associate in the Philpot Lab.
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