A Missense Mutation in a Highly Conserved Alternate Exon of Dynamin-1 Causes Epilepsy in Fitful Mice (original) (raw)
Figure 1
Fitful mice have seizures and neurosensory defects.
(A) Differential traces from EEG recording of fitful heterozygotes. Behavioral events associated with the EEG are shown. Vertical lines are 1s time markings; each channel is approximately 500uV high. (B) Average electroconvulsive thresholds to the minimal forebrain clonic seizure endpoint of B6-Ftfl/+ and B6-+/+ mice at two different stimulus durations (1.0s – left; 0.2s – right). Female and male mice are shown separately. The combined data showed that this modest difference between genotypes in acute seizure threshold was statistically significant (Student's |t|-test, p<0.001). (C) Average latency (# of daily tests) to the first kindled partial seizure following sequential stimulation in B6-+/+ and B6-Ftfl/+ male mice (*Student's |t|-test, p<0.0001). (D) Graph showing the age of onset of observed (behavioral tonic-clonic) seizures in fitful heterozygous mice in the B6 or FVB background. (E) Purkinje cell defect in fitful cerebellum. The upper panels show calbindin antibody staining of wildtype and fitful P15 cerebellum. Notice that the Purkinje cell dendrites are stunted (arrow) in the mutant as compared to wildtype and the soma are less ordered. The lower panels show B6.FVB fitful homozygous and heterozygous Purkinje cells expressing GFP at P17. (F) Auditory brainstem response in fitful and wildtype mice. Left panel: ABR audiograms with average thresholds ± SEM of fitful mouse mutants (open symbols, −/−, n = 14) and their wildtype (n = 5; +/+) and heterozygote (n = 9; +/−) littermates (closed symbols). Right panel: average ABR waveforms (±SEM) of fitful (light grey, n = 9) and wildtype/heterozygous mice (dark grey, n = 9) in response to click stimuli (86 dB, peak equivalent). Latin numbers denominate the ABR peaks.