title: Cytoarchitectural disruption of the superior colliculus and an enlarged acoustic startle response in the Tuba1a mutant mouse.
abstract: The Jenna mutant mouse harbours an S140G mutation in Tuba1a that impairs tubulin heterodimer formation resulting in defective neuronal migration during development. The consequence of decreased neuronal motility is a fractured pyramidal cell layer in the hippocampus and wave-like perturbations in the cerebral cortex. Here, we extend our characterisation of this mouse investigating the laminar architecture of the superior colliculus (SC). Our results reveal that the structure of the SC in mutant animals is intact; however, it is significantly thinner with an apparent fusion of the intermediate grey and white layers. Birthdate labelling at E12.5 and E13.5 showed that the S140G mutation impairs the radial migration of neurons in the SC. A quantitative assessment of neuronal number in adulthood reveals a massive reduction in postmitotic neurons in mutant animals, which we attribute to increased apoptotic cell death. Consistent with the role of the SC in modulating sensorimotor gating, and the circuitry that modulates this behaviour, we find that Jenna mutants exhibit an exaggerated acoustic startle response. Our results highlight the importance of Tuba1a for correct neuronal migration and implicate postnatal apoptotic cell death in the pathophysiological mechanisms underlying the tubulinopathies.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
authors.forename: A
authors.initials: A
authors.lastname: Edwards
authors.forename: C D
authors.initials: CD
authors.lastname: Treiber
authors.forename: M
authors.initials: M
authors.lastname: Breuss
authors.forename: R
authors.initials: R
authors.lastname: Pidsley
authors.forename: G-J
authors.initials: GJ
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Cleak
authors.forename: P L
authors.initials: PL
authors.lastname: Oliver
authors.forename: J
authors.initials: J
authors.lastname: Flint
authors.forename: D A
authors.initials: DA
authors.lastname: Keays
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics*; D013477:Superior Colliculi / Q000473:pathology* / Q000503:physiopathology; D014404:Tubulin / Q000235:genetics*
chemical_list: C569741:Tuba1a protein, mouse; D014404:Tubulin