Nervous system development and function is critically dependent upon its microtubule-based cytoskeleton. Microtubules are assembled from multiple ?- and ?-tubulin isotypes which are encoded by separate, evolutionarily conserved genes. Recently, mutations in the Tubulin ?4 family (Tubb4a and Tubb4b) have been associated with a spectrum of neurological disorders in patients by sequencing studies. How mutations in the Tubb4 genes cause these disorders is not understood. We have generated mouse models for Tubb4-related developmental disorders. Our studies will lead to insights into the mechanisms of the human disease spectrum, as well as to fundamental information on the role of microtubules in mammalian neural development and function.
Tubb4 genes have been recently associated with a spectrum of neurological disorders through patient sequencing studies. We have generated a novel mouse models for Tubb4 will characterize the genetic and molecular mechanisms of how neurological disease develops. These studies will give insights into the human diseases and could inform on the possible therapeutic approaches.
