Quantitative Trait Loci for murine cerebroventricular size
Corinna C. Zygourakis, Glenn D. Rosen
Charles A. Dana Research Institute, Division of Behavioral Neurology,
Department of Neurology, Beth Israel Deaconess Medical Center, 330
Brookline Avenue, Boston MA 02215
Harvard Medical School, Boston, MA
02115
ABSTRACT
Hydrocephalus can lead to serious cognitive and motor deficiencies in
humans and animals. In this study, we map quantitative trait loci
modulating cerebroventricular size in mice. We hypothesize that genes
underlying hydrocephalus might also modulate normal variation in
ventricular size. Using digital images of mouse brain sections and
stereological techniques, we estimated the volume of the entire brain
as well as the volume of the lateral and 3rd ventricles combined in
228
AXB and BXA recombinant inbred mice and their parent strains.
Ventricle
size, expressed as percent of entire brain volume, is a heritable
trait
(h2=0.30). and linkage analysis found a significant quantitative
locus
(QTL) for this phenotype on chromosome 4. Suggestive QTLs on
chromosomes 8 and 13 were also identified. These linkages are further
supported by their close proximity to the Nfia, hy-3, and Foxc1 genes
respectively, previously shown to modulate hydrocephalus (and other
abnormalities) in mice. Epistatic interactions, primarily between
loci
on chromosomes 4 and 7, also affected ventricular size. The results
presented here suggest that ventricular size is a polygenic trait
modulated by epistatic gene interactions.