Fig. 1: Phenotype of G592R Kv3.3 knock-in mice.

a Quantification of numbers of neuronal nuclei per mg of fixed cerebellar tissue (n = 7 wild type; n = 5 G592R Kv3.3 11-month-old animals. Data are mean ± SEM. Two-tailed unpaired t test). b Rota-rod analysis of wild type and mutant mice demonstrating that G592R Kv3.3 mutant animals have significant impairments (wild type at 4 months (females), n = 13; G592R mice at 4 months (females), n = 8; wild type at 7 months (males), n = 9; G592R mice at 7 months (males), n = 17). Data are mean ± SEM, two-tailed unpaired t test. c Comparison of performance of wild type and mutant mice on the dowel walking test, (wild type, n = 6 at 7 months (males); G592R Kv3.3 mice, n = 6; at 7 months (males). Data are mean ± SEM, two-tailed unpaired t test. d Heat map of power distribution in different frequency bands of local field potentials at different depths in the cerebellar vermis of wild type and mutant mice. Quantification of power in frequency bands; delta (e), theta (f), alpha (g), beta (h), gamma (i) and GBO (j) in wild type and G592R Kv3.3 mice. Data for (e–j) are mean ± SEM, two-tailed paired t test (wild type, n = 4; G592R mutant, n = 4). k Western blot and group data for Kv3.3 expression in cerebella of wild type and mutant mice. Kv3.3 abundance was normalized to GAPDH (wild type, n = 3; G592R mutant, n = 3, data are mean ± SEM, two-tailed paired t test). l Light level immunostaining of Kv3.3 using diaminobenzidine labeling in cerebellar Purkinje neurons of wild type and mutant mice. m Low power EM using diaminobenzidine to localize Kv3.3 in Purkinje cells (PC). n Higher power image from a wild type animal showing Kv3.3 immunoreactivity at sites where mitochondria are apposed to the plasma membrane. o As n but showing a small Kv3.3-immunoreactive protrusion. p Examples of Kv3.3 immunoreactive protrusions, some containing membrane-bound organelles, in Purkinje neurons from G592R Kv3.3 mice. l–p are representative of 33 and 31 images taken from sections of three wild-type and three mutant mice, respectively. Source data and uncropped Western blots are provided as a Source Data file.