HGprt deficiency disrupts dopaminergic circuit development in a genetic mouse model of Lesch-Nyhan disease.

ABSTRACT: In Lesch-Nyhan disease (LND), deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase (HGprt) leads to a characteristic neurobehavioral phenotype dominated by dystonia, cognitive deficits and incapacitating self-injurious behavior. It has been known for decades that LND is associated with dysfunction of midbrain dopamine neurons, without overt structural brain abnormalities. Emerging post mortem and in vitro evidence supports the hypothesis that the dopaminergic dysfunction in LND is of developmental origin, but specific pathogenic mechanisms have not been revealed. In the current study, HGprt deficiency causes specific neurodevelopmental abnormalities in mice during embryogenesis, particularly affecting proliferation and migration of developing midbrain dop

SUBMITTER: Witteveen JS 

PROVIDER: S-EPMC9167210 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature