HPRT-APRT-DEFICIENT MICE ARE NOT A MODEL FOR LESCH-NYHAN SYNDROME

Complete hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficie ncy in humans results in the Lesch-Nyhan syndrome which is characteriz ed, among other features, by compulsive self-injurious behavior, HPRT- deficient mice generated using mouse embryonic stem cells exhibit none of the behavioral symptoms associated with the Lesch-Nyhan syndrome, Administration of drugs that inhibit adenine phosphoribosyltransferase (APRT) in HPRT-deficient mice has produced the suggestion that defici ency of APRT in combination with HPRT-deficiency in mice may lead to s elf-mutilation behavior [C. L. Wu and D. W. Melton (1993) Nature Genet , 3, 235-240], To test this proposition, we bred HPRT-APRT-deficient m ice, Although the doubly-deficient mice excrete adenine and its highly insoluble derivative, 2,8-dihydroxyadenine, which are also associated with human APRT deficiency, additional abnormalities or any self-inju rious behavior were not detected, Thus, APRT-HPRT-deficient mice, whic h are devoid of any purine salvage pathways, show no novel phenotype a nd are not a model for the behavioral abnormalities associated with th e Lesch-Nyhan syndrome as previously suggested.