Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D.
Document Type
Article
Publication Date
6-1-2024
Original Citation
Tadenev A,
Hatton C,
Burgess RW.
Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D. J Peripher Nerv Syst. 2024;29(2):213-20.
Keywords
JMG, SS1, Animals, Charcot-Marie-Tooth Disease, Histone Deacetylase 6, Disease Models, Animal, Mice, Humans, Sciatic Nerve, Mice, Knockout, Gene Deletion, Male, Tubulin, Glycine-tRNA Ligase, Neural Conduction
JAX Source
J Peripher Nerv Syst. 2024;29(2):213-20.
ISSN
1529-8027
PMID
38551018
DOI
https://doi.org/10.1111/jns.12623
Grant
National Cancer Institute; National Institute of Neurological Disorders and Stroke; Charcot- Marie-Tooth Association; NIH, Grant/Award Numbers: CA34196, R37NS054154
Abstract
BACKGROUND: Inhibition of HDAC6 has been proposed as a broadly applicable therapeutic strategy for Charcot-Marie-Tooth disease (CMT). Inhibition of HDAC6 increases the acetylation of proteins important in axonal trafficking, such as α-tubulin and Miro, and has been shown to be efficacious in several preclinical studies using mouse models of CMT.
AIMS: Here, we sought to expand on previous preclinical studies by testing the effect of genetic deletion of Hdac6 on mice carrying a humanized knockin allele of Gars1, a model of CMT-type 2D.
METHODS: Gars1
RESULTS: The genetic deletion of Hdac6 increased α-tubulin acetylation in the sciatic nerves of both wild-type and Gars1
INTERPRETATION: Our results differ from those of two previous studies that demonstrated the benefit of the HDAC6 inhibitor tubastatin A in mouse models of CMT2D. While we cannot fully explain the different outcomes, our results offer a counterexample to the benefit of inhibiting HDAC6 in CMT2D, suggesting additional research is necessary.