Slc6a3 Knockin mouse models

Dopamine clearance depends on Slc6a3, the mouse ortholog of human SLC6A3, encoding the dopamine transporter, an SLC6 sodium and chloride coupled symporter with LeuT architecture concentrated on midbrain dopaminergic terminals in striatum, where it sets extracellular dopamine lifetime, supports vesicular refilling, serves as the primary molecular target of cocaine, amphetamine, and methylphenidate, and provides the route of MPP+ entry that confers selective nigral vulnerability. Biallelic loss of function causes dopamine transporter deficiency syndrome with infantile parkinsonism-dystonia, and common variation has been linked to ADHD phenotypes. Slc6a3 knockout mice are viable but hyperdopaminergic, hyperactive, growth retarded, and insensitive to cocaine reward, and the locus is also the standard site for DAT-Cre and DAT-CreERT2 knockin drivers, which must be chosen carefully because some cassettes reduce transporter expression. Match allele class to endpoint, using patient missense knockins for trafficking-defect mechanisms and humanization for inhibitor pharmacology.

An engineered Slc6a3 allele can introduce a human coding region, a point change, or a fluorescent reporter without random transgene integration noise.