{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:11:25Z","timestamp":1792033885040,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002721","name":"Charcot-Marie-Tooth Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA34196"],"award-info":[{"award-number":["CA34196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37NS054154"],"award-info":[{"award-number":["R37NS054154"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inhibition of HDAC6 has been proposed as a broadly applicable therapeutic strategy for Charcot\u2013Marie\u2013Tooth disease (CMT). Inhibition of HDAC6 increases the acetylation of proteins important in axonal trafficking, such as \u03b1\u2010tubulin and Miro, and has been shown to be efficacious in several preclinical studies using mouse models of CMT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>Here, we sought to expand on previous preclinical studies by testing the effect of genetic deletion of <jats:italic>Hdac6<\/jats:italic> on mice carrying a humanized knockin allele of <jats:italic>Gars1<\/jats:italic>, a model of CMT\u2010type 2D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>Gars1<\/jats:italic><jats:sup>\u0394ETAQ<\/jats:sup> mice were bred to an <jats:italic>Hdac6<\/jats:italic> knockout strain, and the resulting offspring were evaluated for clinically relevant outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The genetic deletion of <jats:italic>Hdac6<\/jats:italic> increased \u03b1\u2010tubulin acetylation in the sciatic nerves of both wild\u2010type and <jats:italic>Gars1<\/jats:italic><jats:sup>\u0394ETAQ<\/jats:sup> mice. However, when tested at 5\u2009weeks of age, the <jats:italic>Gars1<\/jats:italic><jats:sup>\u0394ETAQ<\/jats:sup> mice lacking <jats:italic>Hdac6<\/jats:italic> showed no changes in body weight, muscle atrophy, grip strength or endurance, sciatic motor nerve conduction velocity, compound muscle action potential amplitude, or peripheral nerve histopathology compared to <jats:italic>Gars1<\/jats:italic><jats:sup>\u0394ETAQ<\/jats:sup> mice with intact <jats:italic>Hdac6<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12623","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T07:53:20Z","timestamp":1711698800000},"page":"213-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lack of effect from genetic deletion of <i>Hdac6<\/i> in a humanized mouse model of CMT2D"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0801-8267","authenticated-orcid":false,"given":"Abigail L. D.","family":"Tadenev","sequence":"first","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney L.","family":"Hatton","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9229-3407","authenticated-orcid":false,"given":"Robert W.","family":"Burgess","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2013.01.009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000735"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1974.tb00638.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes5010013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.106"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308826"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146533"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146539"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.146692"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.4868"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/417455a"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201702187"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.4.2440"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx375"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2396"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15231"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03461-z"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113281"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/375039"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.08.027"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26501"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1727"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.005"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx058"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22210"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202101308"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130600"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201901099"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01893"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01776"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-11-04170.1997"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010149"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1762-15.2016"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-058-8_20"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.009"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002399"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.002527"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb3414"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.157191"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22691-2"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101867"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054720"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns.12623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T05:46:50Z","timestamp":1719208010000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns.12623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/jns.12623"],"URL":"https:\/\/doi.org\/10.1111\/jns.12623","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"value":"1085-9489","type":"print"},{"value":"1529-8027","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]},"assertion":[{"value":"2024-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}