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‘Housekeeping’ Gene Important for Neurogenesis

Last Updated: August 24, 2009.

Deficiency of the gene responsible for a rare neurological disease, that was thought to be merely important in metabolism, leads to abnormal development of dopaminergic neurons and may explain some of the pathology of the disease, according to a study published online Aug. 11 in Molecular Therapy.

MONDAY, Aug. 24 (HealthDay News) -- Deficiency of the gene responsible for a rare neurological disease, that was thought to be merely important in metabolism, leads to abnormal development of dopaminergic neurons and may explain some of the pathology of the disease, according to a study published online Aug. 11 in Molecular Therapy.

To investigate how mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene causes Lesch-Nyhan disease, Ghiabe-Henri Guibinga, Ph.D., and colleagues from the University of California San Diego in La Jolla examined the effect of HPRT deficiency in embryonic cells undergoing neurogenesis.

The researchers found abnormal expression of several transcription factors and markers of dopaminergic neurons during neuronal differentiation. Although neurite outgrowth was impaired considerably during differentiation, the resulting neurons had normal electrophysiological properties.

"Our present results not only lend the first experimental support to the hypothesis that aberrant development of dopaminergic neurons per se may contribute significantly to the pathology of HPRT deficiency in the human, but, even more importantly, we propose that they suggest that a 'housekeeping gene,' such as HPRT, conventionally considered merely to have important metabolic functions, may also play a vital role in some pathways of mammalian development, including neurogenesis," Guibinga and colleagues conclude.

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