@article{8fc6becdcf2a45c1b676d77b09248d98,
title = "Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration",
abstract = " 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. Latremoliere et al. show that the neuronal-specific tubulin isoform TUBB3 is not required for normal development and function of the nervous system. Lack of TUBB3 decreases the dynamics of microtubules in growth cones, and this reduces axonal growth after peripheral nerve injury and strongly delays functional recovery.",
keywords = "TUBB3, axonal growth, development, diffusion tensor imaging, microtubule dynamics, mouse, post-translational modifications, sensory recovery, spot culture, tubulin",
author = "Alban Latremoliere and Long Cheng and Michelle DeLisle and Chen Wu and Sheena Chew and Hutchinson, {Elizabeth B.} and Andrew Sheridan and Chloe Alexandre and Frederic Latremoliere and Sheu, {Shu Hsien} and Sara Golidy and Takao Omura and Huebner, {Eric A.} and Yanjie Fan and Whitman, {Mary C.} and Elaine Nguyen and Crystal Hermawan and Carlo Pierpaoli and Tischfield, {Max A.} and Woolf, {Clifford J.} and Engle, {Elizabeth C.}",
note = "Funding Information: We thank Laura Anne Lowrey and Garrett Cammarata for technical assistance, the Assay Development & Screening Facility, the Neurodevelopmental Behavior, and the Viral Core of the Boston Children's Hospital IDDRC (NIH; 1U54HD090255), the Histology and Electron Microscopy Cores of Harvard Medical School, the NIH Intramural Program, the Section for Quantitative Imaging and Tissue Sciences (NICHD/NIH), and the NIH Mouse Imaging Facility. This work was supported by the HHMI Medical Fellows Program and Harvard Medical School (to S.C.); the HHMI EXROP Program (to S.G.); the Harvard College Research Program (to A.S.); a Congressionally Directed Medical Research Programs (CDMRP) Award (W81XWH-13-2-0019) (to E.B.H.); the NIH (5T32HL110852-05 to S.-H.S.; K08EY027850 to M.C.W.); a Children's Hospital Ophthalmology Foundation Faculty Discovery Award (to M.C.W.); and the NIH (R01DE022912) and the Dr. Miriam and Sheldon M. Adelson Medical Research Foundation (to C.J.W.). E.C.E. is a Howard Hughes Medical Institute Investigator. Funding Information: We thank Laura Anne Lowrey and Garrett Cammarata for technical assistance, the Assay Development & Screening Facility, the Neurodevelopmental Behavior, and the Viral Core of the Boston Children{\textquoteright}s Hospital IDDRC ( NIH ; 1U54HD090255 ), the Histology and Electron Microscopy Cores of Harvard Medical School, the NIH Intramural Program, the Section for Quantitative Imaging and Tissue Sciences (NICHD/NIH), and the NIH Mouse Imaging Facility. This work was supported by the HHMI Medical Fellows Program and Harvard Medical School (to S.C.); the HHMI EXROP Program (to S.G.); the Harvard College Research Program (to A.S.); a Congressionally Directed Medical Research Programs (CDMRP) Award ( W81XWH-13-2-0019 ) (to E.B.H.); the NIH ( 5T32HL110852-05 to S.-H.S.; K08EY027850 to M.C.W.); a Children{\textquoteright}s Hospital Ophthalmology Foundation Faculty Discovery Award (to M.C.W.); and the NIH ( R01DE022912 ) and the Dr. Miriam and Sheldon M. Adelson Medical Research Foundation (to C.J.W.). E.C.E. is a Howard Hughes Medical Institute Investigator. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = aug,
day = "14",
doi = "10.1016/j.celrep.2018.07.029",
language = "English (US)",
volume = "24",
pages = "1865--1879.e9",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}