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To investigate the roles of Pten and β-Catenin in the midbrain, either the  Pten  gene or the  β-catenin  gene was conditionally ablated, using  Dmbx1  ( d iencephalon/ m esencephalon-expressed  b rain homeobo x  gene 1) -Cre  mice. Homozygous disruption of the  Pten  or  β-catenin  gene in  Dmbx1 -expressing cells caused severe hydrocephalus and mortality during the postnatal period. Conditional deletion of  Pten  resulted in enlargement of midbrain structures.  β-catenin  conditional mutant mice showed malformation of the superior and inferior colliculi and stenosis of the midbrain aqueduct. These results demonstrate that both Pten and β-Catenin are essential for proper midbrain development, and provide the direct evidence that mutations of both  Pten  and  β-catenin  lead to hydrocephalus.

Hydrocephalus caused by conditional ablation of the Pten or beta-catenin gene