A dominant tubulin mutation causes cerebellar neurodegeneration in a genetic model of tubulinopathy.

ABSTRACT: Mutations in tubulins cause distinct neurodevelopmental and degenerative diseases termed "tubulinopathies"; however, little is known about the functional requirements of tubulins or how mutations cause cell-specific pathologies. Here, we identify a mutation in the gene Tubb4a that causes degeneration of cerebellar granule neurons and myelination defects. We show that the neural phenotypes result from a cell type-specific enrichment of a dominant mutant form of Tubb4a relative to the expression other β-tubulin isotypes. Loss of Tubb4a function does not underlie cellular pathology but is compensated by the transcriptional up-regulation of related tubulin genes in a cell type-specific manner. This work establishes that the expression of a primary tubulin mutation in matur

SUBMITTER: Fertuzinhos S 

PROVIDER: S-EPMC8849301 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature