Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the β-amyloid-precursor protein

We previously have reported corpus callosum defects in transgenic mice expressing the β-amyloid precursor protein (βAPP) with a deletion of exon 2 and at only 5% of normal levels. This finding indicates a possible involvement of βAPP in the regulation or guidance of axon growth during neural development. To determine to what degree the βAPP mutation interacts with genetic background alleles that predispose for forebrain commissure defects in some mouse lines, we have assessed the size of the forebrain commissures in a sample of 298 mice. Lines with mixed genetic background were compared with congenic lines obtained by backcrossing to the parental strains C57BL/6 and 129/SvEv. Mice bearing a null mutation of the βAPP gene also were included in the analysis. We show that, independently of genetic background, both lack and underexpression of βAPP are associated with reduced brain weight and reduced size of forebrain commissures, especially of the ventral hippocampal commissure. In addition, both mutations drastically increase the frequency and severity of callosal agenesis and hippocampal commissure defects in mouse lines with 129/SvEv or 129/Ola background.