Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration

Authors
Latremoliere A et al

Lab
Kirby Neurobiology Center, Boston ChildrenÕs Hospital, Boston, MA, USA

Journal
Cell Reports

Abstract
We generated a knockout mouse for the neuronal-specific _-tubulin isoform Tubb3 to investigate its role in nervous system formation and maintenance. Tubb3_/_ mice have no detectable neurobehavioral or neuropathological deficits, and upregulation of mRNA and protein of the remaining _-tubulin isotypes results in equivalent total _-tubulin levels in Tubb3_/_ and wild-type mice. Despite similar levels of total _-tubulin, adult dorsal root ganglia lacking TUBB3 have decreased growth cone microtubule dynamics and a decreased neurite outgrowth rate of 22% inÊvitro and inÊvivo. The effect of the 22% slower growth rate is exacerbated for sensory recovery, where fibers must reinnervate the full volume of the skin to recover touch function. Overall, these data reveal that, while TUBB3 is not required for formation of the nervous system, it has a specific role in the rate of peripheral axon regeneration that cannot be replaced by other _-tubulins.

BIOSEB Instruments Used:
Cold Hot Plate Test (BIO-CHP)