Hydrocephalus in the Otx2+/- mutant mouse.

Mice with the Otx2+/- mutation often die during the postneonatal period. Before death these animals, generated from TT2 ES cells and crossed with CBA mice, develop a dome-shaped head, weakness of the limbs, kyphosis, lethargy, drowsiness, and emaciation. Autopsy of these mice revealed eminent dilatation of lateral ventricles and a ballooned cerebrum. Histological analysis shows edematous change of the periventricular white matter. These results suggest that Otx2 functions as a head organizer, and a mutation of this gene is a likely cause of hydrocephalus in mammals. Additionally, craniobasal skeletal anomaly in half of the heterozygotes and dwarfism in some of the female heterozygotes are described.