| Experiment Id | E-GEOD-27888 | Series Id | GSE27888 |
| Name | Comparative transcriptome analysis of APPs alpha-DM and APLP2-KO brains | Experiment Type | transcription profiling by array |
| Study Type | WT vs. Mutant | Source | ArrayExpress |
| Curation Date | 2017-02-27 |
| description | Despite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and of its proteolytic fragments are still poorly understood. The secreted APPs alpha ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The gamma-secretase generated APP intracellular domain, AICD, functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. Previously, we have generated APPs alpha knockin (KI) mice expressing solely the secreted ectodomain APPs alpha. Here, we generated double mutants (APPs alpha-DM) by crossing APPs alpha-KI mice onto an APLP2-deficient background and show that APPs alpha rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPs alpha-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP. To gain further mechanistic insight into which domains/proteolytic fragments are crucial for hippocampal APP/APLP2 mediated functions, we performed a DNA microarray transcriptome profiling of prefrontal cortex and hippocampus of adult APLP2-KO (APLP2-/-) and APPs alpha-DM mice (APP alpha/alpha; APLP2-/- mice). Interestingly, this analysis failed to reveal major genotype-related transcriptional differences. Expression differences between cortex and hippocampus were, however, readily detectable. Prefrontal cortices and hippocampi of adult mice (38 - 40 weeks) of the following genotypes were analyzed: APLP2-KO (APLP2-/-) (n=3) and APPs alpha-DM (APP alpha/alpha; APLP2-/-) (n=3). |
