Extended Data Fig. 1: The comparative analysis revealed a premature mutation at Trp-187 in mouse Cdk3, which contributes to enhanced instability and markedly elevated expression levels in AD mouse models (APP/PS1) and AD-associated mouse cell lines relative to wild-type controls.
From: CDK3 induces neuronal death and brain atrophy in Alzheimer’s disease
(a) The region containing a single base mutation of Trp-187 to premature mutant residues in CDK3 (in humans) and Cdk3-ps (in mice) is delineated by a rounded box in both mouse and human samples within the basal segment. (b) The CDK3 proteins derived from mice and humans were compared and the premature mutant points (Trp-187 to Term, termed W187*) are marked in the red box. (c-d) The mRNA level of Cdk3-ps was assessed both N2a cells and N2a-APP-695 cells (N2a cell line expressing human APP695 with the Swedish double mutation), as well as WT and APP/PS1 mouse cortical lysates. (e-f) Western blot analysis of CDK3 and CDK3(aa1-186) degradation rate after CHX treatment (200 μM). Quantification of protein levels are shown in o. Three parallel experiments were performed. (n = 3 cases for N2a and N2a-APP-695 respectively in c. Sample sizes in d: Cdk2, n = 12 for both WT and APP/PS1; Cdk3-ps, n = 48 (WT) and n = 36 (APP/PS1). Data represented mean ± SEM. p < 0.05 indicates significance between the two indicated groups. c, d: two-way ANOVA with Tukey post hoc test.).
