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. 2018 May 16;38(20):4774–4790. doi: 10.1523/JNEUROSCI.0360-18.2018

Figure 1.

Figure 1.

Single, double, and triple Cbln1, Cbln2, and Cbln4 KOs do not impair survival, but Cbln1 KOs cause weight loss and Cbln1/2 dKOs induce seizures. A, Images illustrating the body size of littermate control (Ctl), Cbln1 KO, Cbln2 KO, and Cbln1/2 dKO mice at 2 and 12 months of age. Twelve-month-old dKO mice were significantly smaller than age- and sex-matched Ctl, Cbln1KO, and Cbln2KO mice and exhibited spinal changes (arrow in right), which were absent in Ctl littermates. B, Comparison of the weights of single versus double Cbln1/2 KO mice. Cbln1 KO (n = 8) and Cbln1/2 dKO mice (n = 13) weighed significantly less than Ctl (n = 10) and Cbln2 KO mice (n = 9) at 4, 5, and 6 months of age (****p < 0.0001, two-way ANOVA). dKO mice also weighed significantly less than Cbln1 KO mice at 6 months (p = 0.0206, two-tailed t test); however, this difference lost significance after correcting for multiple comparisons of all groups (adjusted p = 0.0934, Tukey's post hoc test). Data are shown as means ± SEM. C, Comparison of the weights of Cbln1, Cbln2, and Cbln4 dKO versus tKO mice. Male Cbln1/2 dKO (n = 6) and Cbln1/2/4 tKO (n = 6) mice weighed significantly less than Ctl (n = 8) littermate mice beginning at 3 months of age; female dKO (n = 8) and tKO (n = 5) mice weighed less than Ctl (n = 8) littermates beginning at 5 months of age, but tKO and dKO mice of either gender did not differ from each other (****p < 0.0001, two-way ANOVA). Data are shown as means ± SEM. D, Cerebellin deletions do not impair mouse survival despite severe motor dysfunction and weight loss. Cbln1/2 dKO (n = 14 at 1 month; n = 13 at 8–12 months) and Cbln1/2/4 tKO mice (n = 11) have normal lifespans compared with Ctl mice (n = 16 at 1 month; n = 15 at 8 months; n = 14 9–12 months). E, Cbln1/2 dKO mice, but not single Cbln1 or Cbln2 KO mice, exhibit a high incidence of seizures. Data show the number of dKO mice that exhibited seizures during two behavioral challenges, whereas no seizures were ever observed in Ctl, Cbln1KO, or Cbln2 KO mice (*p = 0.0368; **p = 0.0015; ***p < 0.0001; Fisher's exact test). F, Cbln1/2/4 tKO mice exhibit a higher seizure propensity than Cbln1/2 dKO mice and seizures emerge earlier in tKO mice than in dKO mice. Data depict the percentage of dKO (n = 14) and tKO (n = 11) mice that exhibited epileptogenic activity during a 3 min tail suspension assay at the indicated ages (p = 0.0001, Mantel–Cox). No seizures were ever observed in Ctl mice (n = 16).