HYDROCEPHALUS IN THE OTX2(+ -) MUTANT MOUSE

Mice with the Otx2(+/-) mutation often die during the postneonatal per iod, Before death these animals, generated from TT2 ES cells and cross ed with CBA mice, develop a dome-shaped head, weakness of the limbs, k yphosis, lethargy, drowsiness, and emaciation. Autopsy of these mice r evealed eminent dilatation of lateral ventricles and a ballooned cereb rum. Histological analysis shows edematous change of the periventricul ar white matter. These results suggest that Otx2 functions as a head o rganizer, and a mutation of this gene is a likely cause of hydrocephal us in mammals. Additionally, craniobasal skeletal anomaly in half of t he heterozygotes and dwarfism in some of the female heterozygotes are described. (C) 1997 Academic Press.