{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:52:59Z","timestamp":1779929579525,"version":"3.53.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R24 NS098523"],"award-info":[{"award-number":["R24 NS098523"]}],"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":["R01 NS102414"],"award-info":[{"award-number":["R01 NS102414"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Charcot\u2013Marie\u2013Tooth disease is an inherited peripheral neuropathy that is clinically and genetically heterogenous. Mutations in IGHMBP2, a ubiquitously expressed DNA\/RNA helicase, have been shown to cause the infantile motor neuron disease spinal muscular atrophy with respiratory distress type 1 (SMARD1), and, more recently, juvenile-onset Charcot\u2013Marie\u2013Tooth disease type 2S (CMT2S). Using CRISPR-cas9 mutagenesis, we developed the first mouse models of CMT2S [p.Glu365del (E365del) and p.Tyr918Cys (Y918C)]. E365del is the first CMT2S mouse model to be discovered and Y918C is the first human CMT2S allele knock-in model. Phenotypic characterization of the homozygous models found progressive peripheral motor and sensory axonal degeneration. Neuromuscular and locomotor assays indicate that both E365del and Y918C mice have motor deficits, while neurobehavioral characterization of sensory function found that E365del mutants have mechanical allodynia. Analysis of femoral motor and sensory nerves identified axonal degeneration, which does not impact nerve conduction velocities in E365del mice, but it does so in the Y918C model. Based on these results, the E365del mutant mouse, and the human allele knock-in, Y918C, represent mouse models with the hallmark phenotypes of CMT2S, which will be critical for understanding the pathogenic mechanisms of IGHMBP2. These mice will complement existing Ighmbp2 alleles modeling SMARD1 to help understand the complex phenotypic and genotypic heterogeneity that is observed in patients with IGHMBP2 variants.<\/jats:p>","DOI":"10.1093\/hmg\/ddac283","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T14:51:17Z","timestamp":1669128677000},"page":"1276-1288","source":"Crossref","is-referenced-by-count":13,"title":["Clinically relevant mouse models of Charcot\u2013Marie\u2013Tooth type 2S"],"prefix":"10.1093","volume":"32","author":[{"given":"Paige B","family":"Martin","sequence":"first","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Holbrook","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"},{"name":"The University of Maine , Orono, ME 04469 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy N","family":"Hicks","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Hines","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent P","family":"Bogdanik","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , 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, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-8296","authenticated-orcid":false,"given":"Gregory A","family":"Cox","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"2023040610580090600_","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1399-0004.1974.tb00638.x","article-title":"Genetic and clinical aspects of Charcot-Marie-Tooth\u2019s disease","volume":"6","author":"Skre","year":"1974","journal-title":"Clin. 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