QPS Neuropharmacology holds an exclusive license from Probiodrug AG for APPSL x hQC mice, which are crossbreds of APPSL and hQC mice (Jawhar et al., 2011). Both transgenes are under the regulatory control of the Thy1 promoter and both mouse lines have a pure C57BL/6xDBA background.
The cross breeding of APPSL and hQC mice results in an increased generation of N-terminal modified pGlu Aβ peptides and allows the analysis of neurodegenerative events that depend on specific pGlu Aβ enzymatic activity in vivo. These mice are an efficient model to analyze pGlu Aβ modifying drugs in vivo. Additionally, double transgenic APPSL x hQC mice present with the same pathologies as APPSL mice, like plaque formation, neuroinflammation and cognitive deficits, but most symptoms appear a little earlier as in single transgenic APPSL mice. This model presents with an unchanged motor performance.
APPSL x hQC mice are thus a good tool to study pGlu Aβ dependent effects on cognition and histological parameters at an early age of 6 months. An additional readout of APPSL x hQC mice are hQC levels.
Figure 1: Morris water maze of 6 month old APPSL x hQC mice compared to non-transgenic littermates. Escape latency in seconds. Mean ± SEM. n = 4-8. Two-way ANOVA with Bonferroni’s post hoc test. **p<0.01; ***p<0.001.
Figure 2: pGluAβ levels in the cortex of APPSL x hQC mice over age. Aβ3(pE)-40/42 quantification (>150 µm² plaque size) with an anti human pGlu Aβ antibody. Mean + SEM. One-way ANOVA. *p<0.05, ***p<0.001. n = 4 – 8.