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 4a (Tubb4a) have been associated with a spectrum of neurological disorders in patients by sequencing studies. How mutations in the Tubb4a gene cause these disorders is not understood. We have generated a mouse model for Tubb4a-related developmental disorders from a forward genetic screen. 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.
Tubb4a has been recently associated with a spectrum of neurological disorders through patient sequencing studies. We have generated a novel mouse model for tubb4a 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.
