Chronologic changes of cerebral ventricular size in a transgenic model of hydrocephalus

We have maintained a transgenic mouse model of hydrocephalus created to ove rproduce the cytokine, transforming growth factor-beta1 (TGF-beta1) in the central nervous system (CNS), The aim of the present study was to estimate the embryonic period when the transgenic mice would develop hydrocephalus, by investigating the chronological developmental changes of the cerebral ve ntricles. Qualitative analysis of ventricular size was performed on section s cut in the coronal plane of embryos at the 15th (E15) and 18th (E18) embr yonic days, and postnatal mice aged 4 days (P4). The presence of the TGF-be ta1 transgene was determined by performing polymerase chain reaction (PCR) analysis. We have examined 24 embryos and 14 postnatal mice. By performing PCR analysis, the TGF-beta1 transgene was determined to be present in 16 (4 2.1%), Five of 16 embryos at E15 carried the transgene, and showed a slight enlargement of the lateral ventricles, Three of 8 embryos at E18 carried t he transgene, and had remarkable enlargement of the lateral ventricles. Eig ht of 14 pups at P4 carried the transgene, and 7 of 8 pups with the transge ne developed hydrocephalus, In pups that were positive for the transgene, m assive enlargement of the lateral ventricles was observed and there was an associated thinning of the overlying cerebral cortex. These results suggest that congenital hydrocephalus may develop at an important embryonic time p eriod, which coincides with the stage of neural stem cell proliferation and differentiation in the CNS. Copyright (C) 2000 S. Karger AG, Basel.