Slc6a1 Conditional Knockout mouse models

GABA reuptake at cortical synapses is mediated by Slc6a1, the mouse ortholog of human SLC6A1, encoding GAT-1, a twelve-transmembrane sodium and chloride dependent symporter of the SLC6 family with the LeuT fold, expressed on GABAergic axon terminals and on astrocytes, where it terminates phasic inhibition and constrains ambient GABA and tonic conductance. It is the pharmacological target of tiagabine. Heterozygous SLC6A1 missense and truncating variants cause myoclonic atonic epilepsy, absence seizures, autism, and intellectual disability, and importantly many missense alleles act through misfolding and ER retention rather than pure haploinsufficiency, which strongly favors patient knockin over simple null when mechanism is the question. Slc6a1 knockout mice are viable with tremor, ataxia, elevated tonic inhibition, and altered seizure susceptibility. Use conditional alleles with neuronal versus astrocytic Cre drivers to separate the two GAT-1 pools, and humanized alleles when chaperone or oligonucleotide therapeutics are tested.

Slc6a1 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.