Quantitative trait loci modulate ventricular size in the mouse brain

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Abstract
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 markersD8Mit94andD8Mit189. We also detected a strong epistatic interaction affecting ventricular volume between loci on Chr 4 (nearD4Mit237andD4Mit214) and on Chr 7 (D7Mit178andD7Mit191). These three QTLs, labeledVent8a,Vent4b, andVent7c, are close to genes that have been previously implicated in hydrocephalus. J. Comp. Neurol. 461:362–369, 2003.