Quantitative trait loci modulate ventricular size in the mouse brain

Cerebral ventricular size in humans varies significantly. Abnormal enlargement of the ventricles has been associated with schizophrenia, and hydrocephalus can lead to serious cognitive and motor deficiencies in humans and animals. In this study, we mapped quantitative trait loci (QTLs) modulating cerebroventricular size in mice. We hypothesized that genes underlying hydrocephalus might also modulate normal variation in ventricular size. By using digital images of mouse brain sections and stereological techniques, we estimated the volume of the combined lateral and third ventricles, as well as the volume of the entire brain, in 228 AXB and BXA recombinant inbred mice and their parent strains (A/J and C57BL/6J). Ventricle size, expressed as percentage of brain volume, is a heritable trait (h² = 0.32). We detected a major QTL controlling variance in volume on chromosome (Chr) 8 near the markers D8Mit94 and D8Mit189. We also detected a strong epistatic interaction affecting ventricular volume between loci on Chr 4 (near D4Mit237 and D4Mit214) and on Chr 7 (D7Mit178 and D7Mit191). These three QTLs, labeled Vent8a, Vent4b, and Vent7c, are close to genes that have been previously implicated in hydrocephalus.