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

作者：Latremoliere, Alban; Cheng, Long; DeLisle, Michelle; Wu, Chen; Chew, Sheena; Hutchinson, Elizabeth B.; Sheridan, Andrew; Alexandre, Chloe; Latremoliere, Frederic; Sheu, Shu-Hsien; Golidy, Sara; Omura, Takao; Huebner, Eric A.; Fan, Yanjie; Whitman, Mary C.; Nguyen, Elaine; Hermawan, Crystal; Pierpaoli, Carlo; Tischfield, Max A.; Woolf, Clifford J.; Engle, Elizabeth C.

来源：Cell Reports, 2018, 24(7): 1865-+.

DOI：10.1016/j.celrep.2018.07.029

• SPINAL-CORD-INJURY
• BETA-TUBULIN ISOTYPE
• MICROTUBULE DYNAMICS
• PERIPHERAL-NERVE
• CORTICAL DEVELOPMENT
• GROWTH
• MUTATIONS
• MOTOR
• REGISTRATION
• HYPOTHESIS

We generated a knockout mouse for the neuronal-specific beta-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 beta-tubulin isotypes results in equivalent total beta-tubulin levels in Tubb3(-/-) and wild-type mice. Despite similar levels of total beta-tubulin, adult dorsal root ganglia lacking TUBB3 have decreased growth cone microtubule dynamics and a decreased neurite outgrowth rate of 22% in vitro and in vivo. 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 beta-tubulins.

• 出版日期2018-8-14
• 单位上海交通大学