{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:12:15Z","timestamp":1783152735782,"version":"3.54.6"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"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\/100007251","name":"Missouri Department of Transportation","doi-asserted-by":"publisher","award":["R01 HL153612"],"award-info":[{"award-number":["R01 HL153612"]}],"id":[{"id":"10.13039\/100007251","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T34 GM136493"],"award-info":[{"award-number":["T34 GM136493"]}],"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":["R25GM064120"],"award-info":[{"award-number":["R25GM064120"]}],"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":["T32 GM008396"],"award-info":[{"award-number":["T32 GM008396"]}],"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":["R01NS113765"],"award-info":[{"award-number":["R01NS113765"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spinal muscular atrophy with respiratory distress type I (SMARD1) is a neurodegenerative disease defined by respiratory distress, muscle atrophy and sensory and autonomic nervous system defects. SMARD1 is a result of mutations within the IGHMBP2 gene. We have generated six Ighmbp2 mouse models based on patient-derived mutations that result in SMARD1 and\/or Charcot-Marie Tooth Type 2 (CMT2S). Here we describe the characterization of one of these models, Ighmbp2D564N (human D565N). The Ighmbp2D564N\/D564N mouse model mimics important aspects of the SMARD1 disease phenotype, including motor neuron degeneration and muscle atrophy. Ighmbp2D564N\/D564N is the first SMARD1 mouse model to demonstrate respiratory defects based on quantified plethysmography analyses. SMARD1 disease phenotypes, including the respiratory defects, are significantly diminished by intracerebroventricular (ICV) injection of ssAAV9-IGHMBP2 and the extent of phenotypic restoration is dose-dependent. Collectively, this model provides important biological insight into SMARD1 disease development.<\/jats:p>","DOI":"10.1093\/hmg\/ddab317","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T19:10:34Z","timestamp":1635361834000},"page":"1293-1307","source":"Crossref","is-referenced-by-count":21,"title":["The <i>Ighmbp2<\/i>D564N mouse model is the first SMARD1 model to demonstrate respiratory defects"],"prefix":"10.1093","volume":"31","author":[{"given":"Caley E","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique A","family":"Lorson","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M","family":"Ricardez Hernandez","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zayd","family":"Al Rawi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiude","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Marquez","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-4094","authenticated-orcid":false,"given":"Eric","family":"Villal\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy N","family":"Keilholz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona O","family":"Garro-Kacher","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7729-070X","authenticated-orcid":false,"given":"Toni","family":"Morcos","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Davis","sequence":"additional","affiliation":[{"name":"Animal Modeling Core, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C","family":"Bryda","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Animal Modeling Core, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian L","family":"Lorson","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"2022042214132865000_ref1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/0883073807310989","article-title":"Spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"23","author":"Kaindl","year":"2008","journal-title":"J. Child Neurol."},{"key":"2022042214132865000_ref2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1055\/s-2007-973741","article-title":"Clinical spectrum and diagnostic criteria of infantile spinal muscular atrophy: further delineation on the basis of SMN gene deletion findings","volume":"27","author":"Rudnik-Schoneborn","year":"1996","journal-title":"Neuropediatrics"},{"key":"2022042214132865000_ref3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/ng703","article-title":"Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1","volume":"29","author":"Grohmann","year":"2001","journal-title":"Nat. Genet."},{"key":"2022042214132865000_ref4","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1093\/brain\/awg278","article-title":"Severe infantile neuropathy with diaphragmatic weakness and its relationship to SMARD1","volume":"126","author":"Pitt","year":"2003","journal-title":"Brain"},{"key":"2022042214132865000_ref5","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ana.10755","article-title":"Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"54","author":"Grohmann","year":"2003","journal-title":"Ann. Neurol."},{"key":"2022042214132865000_ref6","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1055\/s-2004-820994","article-title":"Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"35","author":"Rudnik-Schoneborn","year":"2004","journal-title":"Neuropediatrics"},{"key":"2022042214132865000_ref7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jns.2014.09.010","article-title":"The wide spectrum of clinical phenotypes of spinal muscular atrophy with respiratory distress type 1: a systematic review","volume":"346","author":"Porro","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"2022042214132865000_ref8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00401-005-1056-y","article-title":"The ultrastructure of peripheral nerve, motor end-plate and skeletal muscle in patients suffering from spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"110","author":"Diers","year":"2005","journal-title":"Acta Neuropathol."},{"key":"2022042214132865000_ref9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ejpn.2013.11.006","article-title":"Severe phenotypes of SMARD1 associated with novel mutations of the IGHMBP2 gene and nuclear degeneration of muscle and Schwann cells","volume":"18","author":"Jedrzejowska","year":"2014","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"2022042214132865000_ref10","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1093\/hmg\/ddh222","article-title":"Characterization of Ighmbp2 in motor neurons and implications for the pathomechanism in a mouse model of human spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"13","author":"Grohmann","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132865000_ref11","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/hmg\/ddx434","article-title":"Selective vulnerability in neuronal populations in nmd\/SMARD1 mice","volume":"27","author":"Villalon","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132865000_ref12","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/ana.10182","article-title":"Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13","volume":"51","author":"Viollet","year":"2002","journal-title":"Ann. Neurol."},{"key":"2022042214132865000_ref13","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/humu.9241","article-title":"Allelic heterogeneity of SMARD1 at the IGHMBP2 locus","volume":"23","author":"Maystadt","year":"2004","journal-title":"Hum. Mutat."},{"key":"2022042214132865000_ref14","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/humu.20525","article-title":"Clinical and mutational profile in spinal muscular atrophy with respiratory distress (SMARD): defining novel phenotypes through hierarchical cluster analysis","volume":"28","author":"Guenther","year":"2007","journal-title":"Hum. Mutat."},{"key":"2022042214132865000_ref15","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.ajhg.2014.10.002","article-title":"Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2","volume":"95","author":"Cottenie","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"2022042214132865000_ref16","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/jhg.2017.15","article-title":"Clinical diversity caused by novel IGHMBP2 variants","volume":"62","author":"Yuan","year":"2017","journal-title":"J. Hum. Genet."},{"key":"2022042214132865000_ref17","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.nmd.2018.09.008","article-title":"Charcot Marie Tooth disease type 2S with late onset diaphragmatic weakness: an atypical case","volume":"28","author":"Kulshrestha","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"2022042214132865000_ref18","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1038\/s41467-018-06313-y","article-title":"UPF1-like helicase grip on nucleic acids dictates processivity","volume":"9","author":"Kanaan","year":"2018","journal-title":"Nat. Commun."},{"key":"2022042214132865000_ref19","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1093\/nar\/21.8.1761","article-title":"Isolation of cDNA encoding a binding protein specific to 5\u2032-phosphorylated single-stranded DNA with G-rich sequences","volume":"21","author":"Mizuta","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"2022042214132865000_ref20","doi-asserted-by":"crossref","first-page":"11009","DOI":"10.1093\/nar\/gks792","article-title":"The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1","volume":"40","author":"Lim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2022042214132865000_ref21","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1007\/s00018-020-03492-0","article-title":"Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1)","volume":"77","author":"Perego","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"2022042214132865000_ref22","doi-asserted-by":"crossref","first-page":"17463","DOI":"10.1016\/S0021-9258(19)85357-7","article-title":"The human S mu bp-2, a DNA-binding protein specific to the single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region","volume":"268","author":"Fukita","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2022042214132865000_ref23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0378-1119(96)00630-0","article-title":"Evidence for regulation of transcription and replication of the human neurotropic virus JCV genome by the human S(mu)bp-2 protein in glial cells","volume":"185","author":"Chen","year":"1997","journal-title":"Gene"},{"key":"2022042214132865000_ref24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/viro.1998.9588","article-title":"Smubp-2 represses the Epstein-Barr virus lytic switch promoter","volume":"255","author":"Zhang","year":"1999","journal-title":"Virology"},{"key":"2022042214132865000_ref25","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1093\/hmg\/ddp028","article-title":"IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1)","volume":"18","author":"Guenther","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132865000_ref26","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1093\/hmg\/ddp134","article-title":"Biochemical and genetic evidence for a role of IGHMBP2 in the translational machinery","volume":"18","author":"Planell-Saguer","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132865000_ref27","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/BF00293010","article-title":"Neuromuscular degeneration (nmd): a mutation on mouse chromosome 19 that causes motor neuron degeneration","volume":"6","author":"Cook","year":"1995","journal-title":"Mamm. Genome"},{"key":"2022042214132865000_ref28","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/S0896-6273(00)80652-2","article-title":"Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele","volume":"21","author":"Cox","year":"1998","journal-title":"Neuron"},{"key":"2022042214132865000_ref29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.bbrc.2019.10.032","article-title":"Development of a novel severe mouse model of spinal muscular atrophy with respiratory distress type 1: FVB-nmd","volume":"520","author":"Shababi","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2022042214132865000_ref30","doi-asserted-by":"crossref","first-page":"e1500078","DOI":"10.1126\/sciadv.1500078","article-title":"Gene therapy rescues disease phenotype in a spinal muscular atrophy with respiratory distress type 1 (SMARD1) mouse model","volume":"1","author":"Nizzardo","year":"2015","journal-title":"Sci. Adv."},{"key":"2022042214132865000_ref31","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/mt.2016.33","article-title":"Rescue of a mouse model of spinal muscular atrophy with respiratory distress type 1 by AAV9-IGHMBP2 is dose dependent","volume":"24","author":"Shababi","year":"2016","journal-title":"Mol. Ther."},{"key":"2022042214132865000_ref32","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/hmg\/ddh129","article-title":"Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy","volume":"13","author":"Maddatu","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"2022042214132865000_ref33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.nmd.2005.02.005","article-title":"Properties of slow- and fast-twitch muscle fibres in a mouse model of amyotrophic lateral sclerosis","volume":"15","author":"Atkin","year":"2005","journal-title":"Neuromuscul. Disord."},{"key":"2022042214132865000_ref34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.resp.2013.05.025","article-title":"Common mechanisms of compensatory respiratory plasticity in spinal neurological disorders","volume":"189","author":"Johnson","year":"2013","journal-title":"Respir. Physiol. Neurobiol."},{"key":"2022042214132865000_ref35","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.expneurol.2016.05.033","article-title":"Accessory respiratory muscles enhance ventilation in ALS model mice and are activated by excitatory V2a neurons","volume":"287","author":"Romer","year":"2017","journal-title":"Exp. Neurol."},{"key":"2022042214132865000_ref36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.expneurol.2017.10.015","article-title":"Compensatory plasticity in diaphragm and intercostal muscle utilization in a rat model of ALS","volume":"299","author":"Seven","year":"2018","journal-title":"Exp. Neurol."},{"key":"2022042214132865000_ref37","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41592-018-0011-5","article-title":"CRISPR off-target analysis in genetically engineered rats and mice","volume":"15","author":"Anderson","year":"2018","journal-title":"Nat. Methods"},{"key":"2022042214132865000_ref38","doi-asserted-by":"crossref","first-page":"e3468","DOI":"10.1371\/journal.pone.0003468","article-title":"Development of a single vector system that enhances trans-splicing of SMN2 transcripts","volume":"3","author":"Coady","year":"2008","journal-title":"PLoS One"},{"key":"2022042214132865000_ref39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1542\/peds.16.1.81","article-title":"A barometric method for measuring ventilation in newborn infants","volume":"16","author":"Drorbaugh","year":"1955","journal-title":"Pediatrics"},{"key":"2022042214132865000_ref40","first-page":"644","article-title":"A plethysmograph for long-term measurements of ventilation in unrestrained animals","volume":"45","author":"Jacky","year":"1978","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab317\/41727291\/ddab317.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/8\/1293\/43408453\/ddab317.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/8\/1293\/43408453\/ddab317.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T14:14:14Z","timestamp":1650636854000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/31\/8\/1293\/6415525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,2]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,11,2]]},"published-print":{"date-parts":[[2022,4,22]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab317","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,15]]},"published":{"date-parts":[[2021,11,2]]}}}