Development of hydrocephalus in mice expressing the Gi-coupled GPCR Ro1 RASSL receptor in astrocytes

摘要: We developed a transgenic mouse line that expresses the G(i)-coupled RASSL (receptor activated solely by synthetic ligand) Ro1 in astrocytes to study astrocyte-neuronal communication. Surprisingly, we found all transgenics expressing hydrocephalus. analyzed these mice an effort develop new model of hydrocephalus will further our understanding pathophysiology disease. Expression was restricted crossing hGFAP-tTA (tet transactivator behind human glial fibrillary acidic protein promoter) with tetO-Ro1/tetO-LacZ line. This cross produced double-transgenic expressed astrocytes. All double postnatal day 15, whereas single-transgenic littermate controls appeared normal. Hydrocephalic displayed enlarged ventricles, partial denudation ependymal cell layer, altered subcommissural organ morphology, and obliteration cerebral aqueduct. Severely hydrocephalic also had increased levels phospho-Erk GFAP expression. Administration doxycycline breeding pairs suppressed expression onset offspring. animals maintained on dox did not hydrocephalus; however, if taken off at weaning, ventricles within 7 weeks, indicating induces adults. discovered which rate pathogenesis can be controlled enabling both juvenile adult