Behavioral and neurochemical evaluation of a transgenic mouse model of Lesch-Nyhan syndrome

J Neurol Sci. 1988 Sep;86(2-3):203-13. doi: 10.1016/0022-510x(88)90099-8.


Two transgenic strains of mutant mice lacking hypoxanthine-guanidine phosphoribosyltransferase (HPRT) activity were examined behaviorally and neurochemically for phenotypic similarity to the human Lesch-Nyhan syndrome. In this syndrome, male children markedly deficient in the enzyme HPRT develop self-mutilation and severe motoric difficulties, and exhibit a pronounced deficiency of dopamine in the basal ganglia. The HPRT-deficient mice showed no evidence of self-mutilation, no detectable motor impairments on tests selected for sensitivity to basal ganglia dysfunction, and no differences in response to apomorphine. Biochemical analyses revealed significantly lower levels of striatal dopamine in the HPRT-deficient mice than in HPRT normal littermates, but the depletion was only of the order of 19%. The results suggest that mice lacking HPRT activity do not phenotypically resemble children born with the same enzymatic deficiency in part because mutant mouse striatal dopamine levels are not as low as those seen in clinical cases with Lesch-Nyhan disease. In contrast to Lesch-Nyhan children, mice may be able to utilize alternative pathways more effectively to maintain purine and neurotransmitter levels within the ranges required for normal brain development and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Avoidance Learning*
  • Biogenic Amines / analysis*
  • Brain Chemistry*
  • Disease Models, Animal
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Lesch-Nyhan Syndrome / physiopathology*
  • Lesch-Nyhan Syndrome / psychology
  • Mice
  • Mice, Transgenic
  • Motor Activity* / drug effects
  • Mutation
  • Reference Values
  • Reflex
  • Swimming


  • Biogenic Amines
  • Hypoxanthine Phosphoribosyltransferase
  • Apomorphine