title: Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch-Nyhan disease).
abstract: BACKGROUND
  Lesch-Nyhan disease (LND), an X-linked genetic disease caused by complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), is characterized by hyperuricemia and psychiatric disturbance, mainly self-aggressiveness. Literature dates support the hypothesis that dopaminergic deficit and serotonergic excess in the circuit of basal ganglia are responsible for the aggressive behavior. Altered adenosine transport across the membrane of HPRT-deficient lymphocytes has been reported, suggesting adenosine involvement in LND.
  
  
  METHODS
  The expression of several genes related to the adenosinergic system (ADORA1A, ADORA2A, ADORA2B) were studied in the brain of the murine model of LND by real time PCR. Nucleotide levels and enzyme activities possibly involved in adenosine release were also measured.
  
  
  RESULTS
  Studies performed by real time PCR showed 95% increase in ADORA1A expression, 15% decrease in ADORA2A expression, and no change in ADORA2B expression in knockout mice compared to controls. No significant differences were found in the level of nucleotides or enzyme activities between control and mutant mice.
  
  
  CONCLUSIONS
  Our results suggest that adenosine neurotransmission might be involved in the specific neurobehavioral features of LND by increased expression of adenosine A1 receptors.
authors.affiliation: Laboratorio di Genetica Medica, Istituto Malattie Rare Mauro Baschirotto BIRD Foundation Onlus, 36023 Costozza, Vicenza, Italy. matteo.bertelli@birdfoundation.org
authors.forename: Matteo
authors.initials: M
authors.lastname: Bertelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Cecchin
authors.forename: Cristina
authors.initials: C
authors.lastname: Lapucci
authors.forename: Gabriella
authors.initials: G
authors.lastname: Jacomelli
authors.forename: Hyder A
authors.initials: HA
authors.lastname: Jinnah
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Vanna
authors.initials: V
authors.lastname: Micheli
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000378:metabolism*; D007926:Lesch-Nyhan Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D043682:Receptor, Adenosine A1 / Q000235:genetics; D018047:Receptors, Purinergic P1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D018047:Receptors, Purinergic P1; D007041:Hypoxanthine Phosphoribosyltransferase; D000241:Adenosine