Tremor dominant Kyoto (Trdk) rats carry a missense mutation in the gene encoding the SK2 subunit of small-conductance Ca(2+)-activated K(+) channel.

In this study, we characterized and genetically analyzed F344-Trdk/+ heterozygous rats. The rats exhibited a tremor that was especially evident around weaning but persisted throughout life. The tremors of F344-Trdk/+ rats were attenuated by drugs effective against essential tremor (ET) but not drugs used to treat Parkinson's disease-related tremor, indicating that the pharmacological phenotype of F344-Trdk/+ rats was similar to human ET. Using positional candidate approach, we identified the Trdk mutation as a missense substitution (c. 866 T>A, p. I289N) in Kcnn2, which encodes the SK2 subunit of the small-conductance Ca(2+)-activated K(+) channel. In vitro electrophysiological studies revealed that the I289N mutation diminished SK2 channel activity. These findings demonstrate that F344-Trdk/+ rats represent a novel model of ET, and strongly suggest that Kcnn2 is the causative gene for the tremor phenotype in F344-Trdk/+ rats. PMID: 28917524 [PubMed - as supplied by publisher]
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research