A SPECIFIC, NONPROLIFERATIVE ROLE FOR E2F-5 IN CHOROID-PLEXUS FUNCTION REVEALED BY GENE TARGETING

Homozygous E2F-5 knockout embryos and mice have been generated. Althou gh embryonic development appeared normal, newborn mice developed nonob structive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF ) production. Although the CSF-producing choroid plexus displayed norm al cellular organization, it contained abundant electron-lucent epithe lial cells, consistent with excessive CSF secretory activity. Moreover , E2F-5 CNS expression in normal animals was largely confined to the c horoid plexus, Cell cycle kinetics were not perturbed in homozygous kn ockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proli feration, Rather, it affects the secretory behavior of a differentiate d neural tissue.