Accepted_test

The dopaminergic (DA) system has an essential role in regulating various physiological and pathological behaviors. DA synthesis in the brain occurs in two steps from the amino acid L-tyrosine: first, the enzyme tyrosine hydroxylase (TH) converts L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), and then, the enzyme aromatic amino acid decarboxylase converts L-DOPA to DA. Mutations in the TH gene have been implicated in neurological disorders like Parkinson's disease, dystonia, and bipolar disorders.

Given ethical constraints, studying these mutations directly in humans is limited, prompting the use of laboratory rodents as valuable models. The Ensembl genome database identifies 21 single nucleotide polymorphisms (SNPs) in the mouse Th gene, with the C886T mutation leading to the R278H substitution in the TH molecule. This study aims to assess the impact of this mutation on TH activity in the mouse midbrain, the region containing the DA neuron bodies.

The pilot study highlights the significance of the C886T polymorphism in modulating TH activity in the mouse brain. Notably, this mutation is the first common naturally occurring mutation in the mouse Th gene known to affect enzyme activity. This discovery presents promising avenues for further investigation, offering insights into the physiological implications of this mutation in both normal and pathological contexts.