Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice

Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthi ne phosphoribosyltransferase (HPRT), is characterized by a neurological def icit, the etiology of which is still unclear. Evidence has accumulated indi cating that it reflects dopamine deficiency associated with defective arbor ization of dopaminergic dendrites. We monitored the differentiation in vitr o of dopaminergic neurons, cultured from HPRT-deficient knockout mice. The HPRT-deficient dopaminergic neurons exhibited a decelerated rate of outgrow th of dendrites in comparison to that of control neurons resulting, after 8 days in culture, in 32% smaller average total length of dendrites per neur on (P < 0.025). The results suggest that the abnormal dendrite outgrowth in LNS reflects a defective developmental process. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.