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Updated: Aug 7, 2026
Targeted Knockdown of Genes in the Choroid Plexus
Published on: June 16, 2023
Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch-Nyhan disease)
Matteo Bertelli1, Stefano Cecchin, Cristina Lapucci
1Laboratorio di Genetica Medica, Istituto Malattie Rare Mauro Baschirotto BIRD Foundation Onlus, 36023 Costozza, Vicenza, Italy. matteo.bertelli@birdfoundation.org
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.
