Читать книгу Pathology of Genetically Engineered and Other Mutant Mice - Группа авторов - Страница 106

Hydrocephalus is the most common CNS disorder caused by defective cilia, but ciliary involvement should be considered in any mice displaying brain malformations. Neurons and astrocytes have a single nonmotile primary cilium [78]. These cilia have critical roles in neurogenesis [79–81] and CNS development [82]. Normal CNS development is dependent on neuronal migration, which is a complex process involving signaling molecules that integrate intercellular signals with cytoskeletal proteins to initiate migration and nucleokinesis, which include neurotrophins, glutamate receptors, and peroxisome‐derived factors [83]. Dysfunctional primary cilia are responsible for many neurodevelopmental disorders [82], with the cerebellar malformations associated with Joubert syndrome (JBTS), Meckel–Gruber syndrome (MKS) and Bardet–Biedl syndrome (BBS) providing the most conspicuous examples [84]. Mice with a conditional deletion of 270049A03Rik (formerly Talpid3) in the CNS display the hallmark signs of JBTS, which include progressive ataxia, cerebellar hypoplasia, and abnormal decussation of the superior cerebellar peduncles [85].