{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:54:47Z","timestamp":1780106087070,"version":"3.54.0"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T00:00:00Z","timestamp":1603065600000},"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\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD060586"],"award-info":[{"award-number":["R01HD060586"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CureSMA","award":["BUR1617"],"award-info":[{"award-number":["BUR1617"]}]},{"name":"Marshall Heritage Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Spinal muscular atrophy (SMA) is caused by mutation or deletion of survival motor neuron 1 (SMN1) and retention of SMN2 leading to SMN protein deficiency. We developed an immortalized mouse embryonic fibroblast (iMEF) line in which full-length wild-type Smn (flwt-Smn) can be conditionally deleted using Cre recombinase. iMEFs lacking flwt-Smn are not viable. We tested the SMA patient SMN1 missense mutation alleles A2G, D44V, A111G, E134K and T274I in these cells to determine which human SMN (huSMN) mutant alleles can function in the absence of flwt-Smn. All missense mutant alleles failed to rescue survival in the conditionally deleted iMEFs. Thus, the function lost by these mutations is essential to cell survival. However, co-expression of two different huSMN missense mutants can rescue iMEF survival and small nuclear ribonucleoprotein (snRNP) assembly, demonstrating intragenic complementation of SMN alleles. In addition, we show that a Smn protein lacking exon 2B can rescue iMEF survival and snRNP assembly in the absence of flwt-Smn, indicating exon 2B is not required for the essential function of Smn. For the first time, using this novel cell line, we can assay the function of SMN alleles in the complete absence of flwt-Smn.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa229","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T19:22:54Z","timestamp":1602616974000},"page":"3477-3492","source":"Crossref","is-referenced-by-count":14,"title":["Conditional deletion of SMN in cell culture identifies functional SMN alleles"],"prefix":"10.1093","volume":"29","author":[{"suffix":"III","given":"Anton J","family":"Blatnik","sequence":"first","affiliation":[{"name":"Ohio State Biochemistry Program"},{"name":"Biological Chemistry & Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki L","family":"McGovern","sequence":"additional","affiliation":[{"name":"Biological Chemistry & Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh T","family":"Le","sequence":"additional","affiliation":[{"name":"Biological Chemistry & Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra C","family":"Iyer","sequence":"additional","affiliation":[{"name":"Biological Chemistry & Pharmacology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K","family":"Kaspar","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, Nationwide Children's Hospital; Department of Pediatrics, College of Medicine and Public Health, The Ohio State University; and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur H M","family":"Burghes","sequence":"additional","affiliation":[{"name":"Ohio State Biochemistry Program"},{"name":"Biological Chemistry & Pharmacology"},{"name":"Molecular Genetics"},{"name":"Department of Neurology, The Ohio State University Wexner Medical Center, Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"2021032415074257600_ref1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"2021032415074257600_ref2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrn2670","article-title":"Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?","volume":"10","author":"Burghes","year":"2009","journal-title":"Nat. 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