Figure 1.

A mouse model of progressive myoclonus epilepsy type 7

(A) Sequence similarity between mouse Kcnc1 and human KCNC1 including the Arg320 residue (asterisk), which constitutes the fourth positively charged arginine residue of the highly conserved S4 voltage sensor of Kv channels.

(B) Survival of wild-type (+/+ mice, n = 21), heterozygous (H/+ [Kcnc1-p.Arg320His/+] mice, n = 32), and homozygous (H/H mice: n = 18) mice.

(C) Representative image of +/+, H/+, and H/H mice at P16. Note the normal size of H/+ relative to +/− mice, with a growth impairment of the H/H mice.

(D) H/H mice are smaller compared to age-matched +/+ and H/+ littermates, while there is no significant weight difference between +/+ and H/+ mice at or before weaning. +/+ mice, n = 54; H/+ mice, n = 47; H/H mice, n = 6.

(E) Representative image demonstrates normal brain size between genotypes at P16.

(F and G) There is no difference between +/+ and H/+ mice in body weight (F) or brain weight (G) at 6 months of age. (F) +/+ mice, n = 30; H/+ mice, n = 29. (G) +/+ mice, n = 23; H/+ mice, n = 24. Data are separated by sex in Figure S2.

(H) Representative image of +/+ and H/+ mouse brains at 6 months of age.

(I) Confocal images of calbindin (a marker of Purkinje cells; red) and DAPI (blue) staining in cerebellum demonstrates normal gross anatomy and cytoarchitecture between +/+ and H/+ mice at 2 and 6 months of age. Scale bars: 400 μm (top) and 50 μm (bottom). See also Figures S2, S3, and S5 and Table S1. Data are presented as mean ± SEM.

Statistical analyses: Mantel-Cox test (B), two-way ANOVA with Šídák’s multiple comparison test (D), and unpaired Student’s t test (F and G). ∗p < 0.05 and ∗∗∗p < 0.001. Exact p values can be found in Table S1.