"This finding is important because a better understanding of the dopamine defect in Lesch Nyhan disease will almost certainly shed light on the similar defect in Parkinson's disease," said Friedmann. "The major difference in these two diseases is that in Parkinson's disease, the dopaminergic neurons degenerate and disappear. In Lesch Nyhan disease, the dopamine neurons are present in more or less normal numbers and locations, but appear to function improperly. Now we know a little more about why that is."

A distinct and severely aberrant neurobehavioral symptom of Lesch Nyhan disease is self-mutilation, associated with severe depletion of the neurotransmitter dopamine in the basal ganglia region of the brain, as well as defective dopamine (DA) uptake. This is demonstrated in both humans and the HPRT-deficient mouse model, even though DA neurons are present in relatively normal numbers and with normal distribution patterns.

The UCSD research identified a number of abnormally expressed genes in HPRT-deficient mice and in human HPRT-deficient fibroblasts or stem cells. This discovery led them to the hypothesis that complex, interacting networks and pathways affect many aspect of central nervous system development, possibly including defects in the development of DA neurons themselves.

Contributors to the paper include Ghiabe-Henri Guibinga and Stephen Hsu of the UC San Diego Department of Pediatrics, Center for Molecular Genetics. The research was funded in part by the National Institutes of Health and the Lesch Nyhan Syndrome Children's Research Foundation.

Source: University of California - San Diego