Jelena Lazovic1, William J. Zinnanti2,
Russell E. Jacobs1
1Biology, California Institute of
Technology, Pasadena, CA, United States; 2Pediatrics, Children's
hospital at SUNY Downstate, Brooklyn, NY, United States
In
recent years white matter abnormalities, including leukoencephalopathy, are
being increasingly recognized in patients suffering from glutaric acidemia
type I (GA-1). The mechanism leading
to leukoencephalopathy remains unknown, as well as the extent of myelin
degradation. In this work we use a
mouse model of GA-1 and combination of MRI, histology and behavioral testing
to establish the basis for abnormal appearance of white matter in this
disorder. Presented data suggest
myelin degradation to be secondary to axonal loss in GA-1. Behavioral data implicate damaged neuronal
populations to be involved in sensory-motor integration.