Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice

Nat Genet. 1993 Mar;3(3):235-40. doi: 10.1038/ng0393-235.

Abstract

The inherited disease Lesch-Nyhan syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan syndrome and the evaluation of novel therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / metabolism
  • Adenine / pharmacology
  • Adenine Phosphoribosyltransferase / metabolism
  • Animals
  • Brain / metabolism*
  • Caffeine / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Embryo, Mammalian
  • Hypoxanthine
  • Hypoxanthine Phosphoribosyltransferase / deficiency*
  • Hypoxanthines / metabolism
  • Lesch-Nyhan Syndrome / enzymology*
  • Lesch-Nyhan Syndrome / genetics
  • Lesch-Nyhan Syndrome / physiopathology
  • Mice
  • Mice, Mutant Strains
  • Purines / metabolism*
  • Self-Injurious Behavior
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / enzymology
  • Thymidine / metabolism

Substances

  • Hypoxanthines
  • Purines
  • 9-ethyladenine
  • Hypoxanthine
  • Caffeine
  • Adenine Phosphoribosyltransferase
  • Hypoxanthine Phosphoribosyltransferase
  • Adenine
  • Thymidine