Lack of effect from genetic deletion of Hdac6 in a humanized mouse model of CMT2D

• DOI: 10.1111/jns.12623
• Publication Date: 2024-03-29T07:53:20Z
• Authors: Abigail L. D. Tad...; Courtney L. Hatton; Robert W. Burgess
• Keywords: HDAC6; Knockout mouse

Abstract Background Inhibition of HDAC6 has been proposed as a broadly applicable therapeutic strategy for Charcot–Marie–Tooth disease (CMT). increases the acetylation proteins important in axonal trafficking, such α‐tubulin and Miro, shown to be efficacious several preclinical studies using mouse models CMT. Aims Here, we sought expand on previous by testing effect genetic deletion Hdac6 mice carrying humanized knockin allele Gars1 , model CMT‐type 2D. Methods ΔETAQ were bred an knockout strain, resulting offspring evaluated clinically relevant outcomes. Results The increased sciatic nerves both wild‐type mice. However, when tested at 5 weeks age, lacking showed no changes body weight, muscle atrophy, grip strength or endurance, motor nerve conduction velocity, compound action potential amplitude, peripheral histopathology compared with intact . Interpretation Our results differ from those two that demonstrated benefit inhibitor tubastatin A CMT2D. While cannot fully explain different outcomes, our offer counterexample inhibiting CMT2D, suggesting additional research is necessary.