Fig. 1.

MIM^EX15 mutants develop progressive spinocerebellar ataxia. (A) The structure of the Mtss1 locus with alternative promoters and the Src interacting domain deleted in MIM^EX15 mutants. (B) Loss of MTSS1 protein in MIM^EX15 cerebellum lysate shown with MTSS1 antibody against the N-terminal I-BAR (IMD) domain. (C and D) MIM^EX15 mice show slower movement velocity (C) and less frequent rearing (D) in open field tests. (E) Impaired rotarod performance in MIM^EX15 mutants is shown as reduced duration (time to fall). (F) A composite test of gait, balance, and grip strength to measure spinocerebellar ataxia symptoms. An increased score reflects reduced function with an age-dependent increase in severity in MIM^EX15 mutants. (G) Age-dependent loss of Purkinje neurons in MIM^EX15 mutants occurs after the onset of ataxia. (H) At 20 wk MIM^Loxp/−;Pcp2-Cre and MIM^Loxp/Loxp;Pcp2-Cre mutants show a dramatic reduction in Purkinje neurons that stain with MTSS1. Many Purkinje neurons persist, as there is a less dramatic reduction in calbindin⁺ Purkinje cell number. *P < 0.05, **P < 0.005, ***P < 5E-5, one-way ANOVA with Tukey post hoc test; ns, not significant. Error bars indicate SEM.