Differential gene expression in ADAM10 over-expressing transgenic mice

In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity. To assess the influence of ADAM10 on the gene expression profile in the brain we performed microarray analysis using RNA isolated from brains of five month old mice over-expressing either the α-secretase ADAM10 or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, 355 genes were found to be differentially expressed in ADAM10 transgenic mice and 143 genes in dnADAM10 mice. A higher number of genes was found to be differentially regulated in double-transgenic mouse strains additionally expressing the human APP V717I mutant (APP[V717I]). Thus, α-secretase cleavage of over-expressed APP[V717I] alters CNS gene expression additionally. Keywords: genetic modification We performed microarray analysis with cDNA transcribed from total RNA of brains from five month old mice. Mono-transgenic ADAM10 as well as dnADAM10 mice were investigated in comparison to non-transgenic FVB/N wild-type mice (n = 3 females), to analyze the influence of the a -secretase ADAM10 or its catalytically inactive form (dnADAM10) on the gene expression profile of the CNS. To elucidate the effect of ADAM10 and dnADAM10 on gene expression we compared samples derived from double-transgenic ADAM10/APP[V717I] and dnADAM10/APP[V717I] mice to those from mono-transgenic APP[V717I] mice (n = 3 females and n = 3 males). At the age of 5 months, APP[V717I] show cognitive deficits, whereas amyloid plaque formation occurs several months later (Moechars et al., 1999). Both were investigated in order to examine an influence of sex. ChipInspector carries out significance analysis on the single probe level. Normalized probe set level data not provided for individual Sample records. Processed data is available on Series record.