| Corpus callosum size in mice is a complex quantitative trait that is influenced by interactions between multiple genes and environmental effects. Identification of genes that influence corpus callosum formation in mice will lead to a better understanding of the mechanisms controlling corpus callosum development and will provide insight for neurodevelopmental disorders presenting with commissure defects.;Previous work has implicated genes on the X chromosome in corpus callosum development. We performed reciprocal crosses between inbred mouse strains BTBR T/+ tf/ff (BTBR), lacking a corpus callosum, and BALB/cByJ (BALB), having a corpus callosum to investigate X chromosome influence on mouse corpus callosum size. We found that the X chromosome derived from BTBR possesses dominant alleles resulting in a decrease in the mean midsagittal area of the corpus callosum. Linkage analysis in backcross progeny subsequently identified two QTLs on the X chromosome that influence corpus callosum size, one at 68.5Mb and the other at 134.5Mb (NCBI Build 34). Global gene expression analyses on total RNA from embryonic day 16.5 brains of reciprocal F1 male mice revealed gene expression differences that are influenced by the X chromosome. Differentially expressed genes within our critical intervals are currently being examined as candidate genes contributing to agenesis of the corpus callosum in BTBR inbred mice.;The function of the corpus callosum in humans and mice is mostly uncharacterized. Identifying changes in cortical gene expression between mice with and without a corpus callosum could lead to new hypotheses about its function. Since corpus callosum size varies in the 129S1/SvImJ (129S1) inbred mouse strain, we have a unique system to study gene expression patterns in the brains of mice with and without a corpus callosum on a genetically identical background. Global gene expression analyses were carried out to determine cortical expression differences between callosal and acallosal 129S1 mice. Our clustering analyses revealed a more symmetrical pattern of gene expression between the left and right cortex in mice having a corpus callosum compared with acallosal mice. |
