A zebrafish model of acmsd deficiency does not support a prominent role for ACMSD in Parkinson's disease.

ABSTRACT: Single nucleotide polymorphisms adjacent to the α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) gene have been associated with Parkinson's disease (PD) in genome-wide association studies (GWAS). However, its biological validation as a PD risk gene has been hampered by the lack of available models. Using CRISPR/Cas9, we generated a zebrafish model of acmsd deficiency with marked increase in quinolinic acid. Despite this, acmsd^-/- zebrafish were viable, fertile, morphologically normal and demonstrated no abnormalities in spontaneous movement. In contrast to the postulated pro-immune pathomechanism linking ACMSD to PD, microglial cells and expression of the proinflammatory cytokines cxcl8, il-1β, and mmp9 were similar between acmsd^-/- and controls. The num

SUBMITTER: Fargher E 

PROVIDER: S-EPMC12064770 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature