title: A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.
abstract: The human Lesch-Nyhan syndrome is a rare neurological and behavioural disorder, affecting only males, which is caused by an inherited deficiency in the level of activity of the purine salvage enzyme hypoxanthine-guanosine phosphoribosyl transferase (HPRT). How the resulting alterations in purine metabolism lead to the severe symptoms characteristic of Lesch-Nyhan patients is still not understood. No mutations at the Hprt locus leading to loss of activity have been described in laboratory animals. To derive an animal model for the Lesch-Nyhan syndrome, we have used cultured mouse embryonic stem cells, mutagenized by retroviral insertion and selected for loss of HPRT activity, to construct chimaeric mice. Two clonal lines carrying different mutant Hprt alleles have given rise to germ cells in chimaeras, allowing the derivation of strains of mutant mice having the same biochemical defect as Lesch-Nyhan patients. Male mice carrying the mutant alleles are viable and analysis of their cells shows a total lack of HPRT activity.
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002678:Chimera; D004262:DNA Restriction Enzymes; D004195:Disease Models, Animal; D005796:Genes; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007926:Lesch-Nyhan Syndrome / Q000235:genetics*; D051379:Mice; D013234:Stem Cells / Q000502:physiology*
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase; D004262:DNA Restriction Enzymes