Impaired striatal dopamine output of homozygous Wfs1 mutant mice in response to [K+] challenge.

Loss of function of the Wfs1 gene causes Wolfram syndrome, a rare multisystem degenerative disorder. Mutant mice with targeted Wfs1 gene disruption (Wfs1 KO) display morphological and behavioral impairments that are not well understood. The present study aimed to investigate the striatal dopamine output of wild-type, heterozygous, and homozygous Wfs1 null-mutant mice using in vivo microdialysis technique. The baseline dopamine output in striatum was similar in all three animal groups. The application of 100 mM [K+]-rich modified Ringer solution caused in homozygous Wfs1 mutant mice an increase of dopamine output by 400%, while in wild-type and heterozygous animals, the increase of the dopamine output yielded up to 1,200%. In sum, the homozygous Wfs1 mutant mice (AUC₀₋₃ = 0.212 nM/μl h) show significantly decreased striatal dopamine output in response to high-concentration [K+] challenge as compared with wild-type or heterozygous Wfs1 mutant conspecifics (AUC₀₋₃ = 0.427 and 0.505 nM/μl h, respectively). This could explain at least some of the behavioral alterations in Wfs1 mutant mice.