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. Author manuscript; available in PMC: 2022 Sep 30.
Published in final edited form as: J Neurosci. 2022 Jul 14;42(33):6453–6468. doi: 10.1523/JNEUROSCI.0521-22.2022

Figure 7. Duplication of the Dp3Tyb region is sufficient to raise the protein abundance of DYRK1A in the cortex but does not significantly alter BACE2, FL-APP or CTF abundance.

Figure 7

The abundance of (A-B) DYRK1A, (A, C) BACE2, (D, E) full-length, APP (FL-APP), (D, F) C-terminal fragment-α (CTF-α) and (D, G) C-terminal fragment-β (CTF-β) relative to β-actin loading control was measured by western blot in the cortex at 3 months of age in male and female mice. ANOVA analysis indicated that an additional copy of the Dp3Tyb region increased the abundance of (B) DYRK1A (F(1,49) = 16.511, p < 0.001) and (C) BACE2 F(1,49) = 4.444, p = 0.040). Post-hoc pair-wise comparison with Bonferroni correction for multiple comparison, demonstrated that significantly higher levels of DYRK1A were oberved in Dp3Tyb;AppNL-F/NL-F compared to AppNL-F/NL-F cortex (p = 0.002) but that BACE2 levels did not differ between these two genotypes of mice (p = 0.359). There was no effect of an extra copy of the Dp3Tyb region on the abundance of (E) FL-APP level (F(1,49) = 2.183, p = 0.126), (F) CTF-α (F(1,40) = 0.040, p = 0.843), or (G) CTF-β (F(1,40) = 0.008, p = 0.929). As previously reported (Saito, Matsuba et al. 2014), mice homozygous for the AppNL-F allele had lower abundance of (E) FL-APP (F(1,49) = 16.790, p < 0.001), (F) CTF-α (F(1,40) = 15.739, p < 0.001) and a higher abundance of (G) CTF-β (F(1,40) = 147.440, p < 0.001). Wild-type (WT) (female n = 6, male n = 11), Dp3Tyb (female n = 5, male n = 7), AppNL-F (female n = 8, male n = 7) and Dp3Tyb;AppNL-F/NL-F (female n = 5, male n = 8). CTF were below the limit of detection in Wild-type (n = 3) Dp3Tyb (n = 1), AppNL-F (n = 2) and Dp3Tyb;AppNL-F/NL-F (n = 3) samples. Error bars show SEM, data points are independent mice. Dp3Tyb abbreviated to Dp3 for clarity.