我们为神经元特异性β-微管蛋白同工型Tubb3制作了敲除小鼠,以研究其在神经系统形成和维持中的作用。Tubb3-/-小鼠没有可检测到的神经行为或神经病理学缺陷,其余β-微管蛋白同种型的mRNA和蛋白质的上调导致Tubb3-/-和野生型小鼠中相同的总β-微管蛋白水平。尽管总β-微管蛋白水平相似,缺乏TUBB3的成年背根神经节在体外和体内均降低了生长锥微管动力学,神经突生长速率降低了22%。22%的生长速度较慢的影响加剧了感官恢复,在那里,纤维必须恢复整个体积的皮肤恢复触摸功能。总的来说,这些数据表明,虽然形成神经系统不需要TUBB3,它在外周轴突再生速率中具有特定的作用,不能被其他β-微管蛋白取代。
We generated a knockout mouse for the neuronal-specific β-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 β-tubulin isotypes results in equivalent total β-tubulin levels in Tubb3-/- and wild-type mice. Despite similar levels of total β-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 β-tubulins.