GM03813
Fibroblast from Skin, Arm
Description:
SPINAL MUSCULAR ATROPHY, TYPE II; SMA2
SURVIVAL OF MOTOR NEURON 1, TELOMERIC; SMN1
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Connective Tissue, Muscle, and Bone |
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Biopsy Source
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Arm
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Arm
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Race
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White
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Country of Origin
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USA
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Family Member
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3
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
4.81 |
| Passage Frozen |
7 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| Gene |
SMN1 |
| Chromosomal Location |
5q12.2-q13.3 |
| Allelic Variant 1 |
exons 7 and 8 deleted; SPINAL MUSCULAR ATROPHY, TYPE I |
| Identified Mutation |
EX7-8DEL |
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| Gene |
SMN1 |
| Chromosomal Location |
5q12.2-q13.3 |
| Allelic Variant 1 |
exons 7 and 8 deleted; SPINAL MUSCULAR ATROPHY, TYPE I |
| Identified Mutation |
EX7-8DEL |
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| Gene |
SMN1 |
| Chromosomal Location |
5q12.2-q13.3 |
| Allelic Variant 2 |
exons 7 and 8 deleted; SPINAL MUSCULAR ATROPHY, TYPE I |
| Identified Mutation |
EX7-8DEL |
| |
| Gene |
SMN1 |
| Chromosomal Location |
5q12.2-q13.3 |
| Allelic Variant 2 |
exons 7 and 8 deleted; SPINAL MUSCULAR ATROPHY, TYPE I |
| Identified Mutation |
EX7-8DEL |
| Remarks |
Clinically affected; born after full term uncomplicated pregnancy; rolled over at 6 months old; began babbling at 9 months old; by 12 months old, there was marked muscle atrophy and weakness; absent deep tendon reflexes; constipation; donor subject has 3 copies of the SMN2 gene (data from several sources including Stabley et al. 2015, PMID 26247043); PCR analysis showed that this donor subject is homozygous for the deletion of exons 7 and 8 in the SMN1 gene; similarly affected brother (not in repository); mother is GM03814 (Fibro)/GM24474 (iPSC); father is GM03815 (Fibro); see GM23240 (iPSC - lentiviral) and GM24468 (iPSC - episomal); previously classified as SMA I, but data such as onset features and SMN2 dosage in the proband supported re-classification to SMA II. |
| Yeoh YQ, Amin A, Cuic B, Tomas D, Turner BJ, Shabanpoor F, Efficient systemic CNS delivery of a therapeutic antisense oligonucleotide with a blood-brain barrier-penetrating ApoE-derived peptide Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie175:116737 2024 |
| PubMed ID: 38749176 |
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| James R, Faller KME, Groen EJN, Wirth B, Gillingwater TH, Altered mitochondrial function in fibroblast cell lines derived from disease carriers of spinal muscular atrophy Communications medicine4:86 2023 |
| PubMed ID: 38750213 |
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| Kordala AJ, Stoodley J, Ahlskog N, Hanifi M, Garcia Guerra A, Bhomra A, Lim WF, Murray LM, Talbot K, Hammond SM, Wood MJ, Rinaldi C, PRMT inhibitor promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue SMA mice EMBO molecular medicine4:e17683 2023 |
| PubMed ID: 37724723 |
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| Ottesen EW, Seo J, Luo D, Singh NN, Singh RN, A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes Nucleic acids research4:e17683 2023 |
| PubMed ID: 38214229 |
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| Ottesen EW, Singh NN, Luo D, Kaas B, Gillette BJ, Seo J, Jorgensen HJ, Singh RN, Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy Nucleic acids research4:e17683 2023 |
| PubMed ID: 37026480 |
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| Januel C, Menduti G, Mamchaoui K, Martinat C, Artero R, Konieczny P, Boido M, Moxifloxacin rescues SMA phenotypes in patient-derived cells and animal model Cellular and molecular life sciences : CMLS79:441 2022 |
| PubMed ID: 35864358 |
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| Lumpkin CJ, Harris AW, Connell AJ, Kirk RW, Whiting JA, Saieva L, Pellizzoni L, Burghes AHM, Butchbach MER, Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy Scientific reports13:10374 2022 |
| PubMed ID: 37365234 |
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| Filer DL, Kuo F, Brandt AT, Tilley CR, Mieczkowski PA, Berg JS, Robasky K, Li Y, Bizon C, Tilson JL, Powell BC, Bost DM, Jeffries CD, Wilhelmsen KC, Pre-capture multiplexing provides additional power to detect copy number variation in exome sequencing BMC bioinformatics22:374 2021 |
| PubMed ID: 34284719 |
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| Sansa A, de la Fuente S, Comella JX, Garcera A, Soler RM, Intracellular pathways involved in cell survival are deregulated in mouse and human spinal muscular atrophy motoneurons Neurobiology of disease155:105366 2021 |
| PubMed ID: 33845129 |
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| Sansa A, Hidalgo I, Miralles MP, de la Fuente S, Perez-Garcia MJ, Munell F, Soler RM, Garcera A, Spinal Muscular Atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons Acta neuropathologica communications9:122 2021 |
| PubMed ID: 34217376 |
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| Toosaranont J, Ruschadaariyachat S, Mujchariyakul W, Arora JK, Charoensawan V, Suktitipat B, Palmer TN, Fletcher S, Wilton SD, Mitrpant C, Antisense Oligonucleotide Induction of the hnRNPA1b Isoform Affects Pre-mRNA Splicing of International journal of molecular sciences23:122 2021 |
| PubMed ID: 35409296 |
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| Ando S, Suzuki S, Okubo S, Ohuchi K, Takahashi K, Nakamura S, Shimazawa M, Fuji K, Hara H, Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy Scientific reports10:17472 2020 |
| PubMed ID: 33060681 |
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| McCormack NM, Abera MB, Arnold ES, Gibbs RM, Martin SE, Buehler E, Chen YC, Chen L, Fischbeck KH, Burnett BG, A high-throughput genome-wide RNAi screen identifies modifiers of survival motor neuron protein Cell reports35:109125 2020 |
| PubMed ID: 33979606 |
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| Hammond SM, Abendroth F, Gait MJ, Wood MJA, Evaluation of Cell-Penetrating Peptide Delivery of Antisense Oligonucleotides for Therapeutic Efficacy in Spinal Muscular Atrophy Methods in molecular biology (Clifton, NJ)2036:221-236 2019 |
| PubMed ID: 31410800 |
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| Kaifer KA, Villalón E, O'Brien BS, Sison SL, Smith CE, Simon ME, Marquez J, O'Day S, Hopkins AE, Neff R, Rindt H, Ebert AD, Lorson CL, AAV9-Mediated Delivery of miR-23a Reduces Disease Severity in Smn2B-/SMA Model Mice Human molecular genetics2036:221-236 2019 |
| PubMed ID: 31211843 |
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| Pagliarini V, Guerra M, Di Rosa V, Compagnucci C, Sette C, Combined treatment with the histone deacetylase inhibitor LBH589 and a splice-switch antisense oligonucleotide enhances SMN2 splicing and SMN expression in Spinal Muscular Atrophy cells Journal of neurochemistry2036:e14935 2019 |
| PubMed ID: 31811660 |
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| Pagliarini V, Jolly A, Bielli P, Di Rosa V, De la Grange P, Sette C, Sam68 binds Alu-rich introns in SMN and promotes pre-mRNA circularization Nucleic acids research2036:e14935 2019 |
| PubMed ID: 31777926 |
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| Patil NA, Karas JA, Turner BJ, Shabanpoor F, Thiol-Cyanobenzothiazole Ligation for the Efficient Preparation of Peptide-PNA Conjugates Bioconjugate chemistry2036:e14935 2019 |
| PubMed ID: 30645945 |
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| Dayangac-Erden D1, Gur-Dedeoglu B2, Eskici FN1, Oztemur-Islakoglu Y2, Erdem-Ozdamar S3., Do Perineuronal Net Elements Contribute to Pathophysiology of Spinal Muscular Atrophy? In Vitro and Transcriptomics Insights OMICS A Journal of Integrative Biology2036:e14935 2018 |
| PubMed ID: 30106667 |
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| Du M, Jillette N, Zhu JJ, Li S, Cheng AW, CRISPR artificial splicing factors Nature communications11:2973 2018 |
| PubMed ID: 32532987 |
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| Garcia-Lopez A1, Tessaro F2, Jonker HRA3, Wacker A3, Richter C3, Comte A4, Berntenis N5, Schmucki R5, Hatje K5, Petermann O2, Chiriano G2, Perozzo R2, Sciarra D2, Konieczny P6,7, Faustino I8, Fournet G4, Orozco M8, Artero R6,7, Metzger F5, Ebeling M5, Goekjian P4, Joseph B4, Schwalbe H3, Scapozza L, Targeting RNA structure in SMN2 reverses spinal muscular atrophy molecular phenotypes Nature Communications
9:2032 2018 |
| PubMed ID: 29795225 |
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| Ottesen EW, Luo D, Seo J, Singh NN, Singh RN, Human Survival Motor Neuron genes generate a vast repertoire of circular RNAs Nucleic acids research9:2032 2018 |
| PubMed ID: 30698797 |
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| Singh NN, Luo D, Singh RN, Pre-mRNA Splicing Modulation by Antisense Oligonucleotides Methods in molecular biology (Clifton, NJ)1828:415-437 2018 |
| PubMed ID: 30171557 |
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| Touznik A, Maruyama R, Yokota T, In Vitro Evaluation of Antisense-Mediated Exon Inclusion for Spinal Muscular Atrophy Methods in molecular biology (Clifton, NJ)1828:439-454 2018 |
| PubMed ID: 30171558 |
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| Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S, Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy Scientific reports8:2075 2017 |
| PubMed ID: 29391529 |
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| Stabley DL, Holbrook J, Harris AW, Swoboda KJ, Crawford TO, Sol-Church K, Butchbach MER, Establishing a reference dataset for the authentication of spinal muscular atrophy cell lines using STR profiling and digital PCR Neuromuscular disorders : NMD27:439-446 2016 |
| PubMed ID: 28284873 |
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| Stabley DL, Harris AW, Holbrook J, Chubbs NJ, Lozo KW, Crawford TO, Swoboda KJ, Funanage VL, Wang W, Mackenzie W, Scavina M, Sol-Church K, Butchbach ME, SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR Molecular genetics & genomic medicine3:248-57 2015 |
| PubMed ID: 26247043 |
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| Xu CC, Denton KR, Wang ZB, Zhang X, Li XJ, Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy Disease models & mechanisms9:39-49 2015 |
| PubMed ID: 26586529 |
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| Mack SG, Cook DJ, Dhurjati P, Butchbach ME, Systems biology investigation of cAMP modulation to increase SMN levels for the treatment of spinal muscular atrophy PloS one9:e115473 2014 |
| PubMed ID: 25514431 |
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| Liu ML, Zang T, Zou Y, Chang JC, Gibson JR, Huber KM, Zhang CL, Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into cholinergic neurons Nature communications4:2183 2013 |
| PubMed ID: 23873306 |
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| Anderton RS, Price LL, Turner BJ, Meloni BP, Mitrpant C, Mastaglia FL, Goh C, Wilton SD, Boulos S, Co-regulation of SMN and Bcl-xL Expression: Implications for Neuroprotection in Spinal Muscular Atrophy Neuroscience4:2183 2012 |
| PubMed ID: 22732506 |
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| Liu J, Hu J, Corey DR, Expanding the action of duplex RNAs into the nucleus: redirecting alternative splicing Nucleic acids research40:1240-50 2011 |
| PubMed ID: 21948593 |
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| Anderton RS, Meloni BP, Mastaglia FL, Greene WK, Boulos S, Survival of motor neuron protein over-expression prevents calpain-mediated cleavage and activation of procaspase-3 in differentiated human SH-SY5Y cells Neuroscience181:226-33 2010 |
| PubMed ID: 21333717 |
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| Ebert, A.D. and Svendsen, C.N., Stem Cell Model of Spinal Muscular Atrophy Arch Neurol67(6):665-669 2010 |
| PubMed ID: 20558385 |
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| Ebert, A.D.; Yu, J.; Ferrill, F.R.; Mattis, V.B.; Lorson, C.L.; Thomson, J.A.; and Svendsen, C.N., Induced pluripotent stem cells from a spinal muscular atrophy patient Nature457(7227):277-80 2009 |
| PubMed ID: 19098894 |
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| Coady TH, Baughan TD, Shababi M, Passini MA, Lorson CL, Development of a single vector system that enhances trans-splicing of SMN2 transcripts PloS one3:e3468 2008 |
| PubMed ID: 18941511 |
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| Thi Man N, Humphrey E, Lam LT, Fuller HR, Lynch TA, Sewry CA, Goodwin PR, Mackenzie AE, Morris GE, A two-site ELISA can quantify upregulation of SMN protein by drugs for spinal muscular atrophy Neurology3:e3468 2008 |
| PubMed ID: 18633133 |
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| Thurmond J1, Butchbach ME, Palomo M, Pease B, Rao M, Bedell L, Keyvan M, Pai G, Mishra R, Haraldsson M, Andresson T, Bragason G, Thosteinsdottir M, Bjornsson JM, Coovert DD, Burghes AH, Gurney ME, Singh J., Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy. J Med Chem51(3):449-69 2008 |
| PubMed ID: 18205293 |
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| Novoyatleva T1, Heinrich B, Tang Y, Benderska N, Butchbach ME, Lorson CL, Lorson MA, Ben-Dov C, Fehlbaum P, Bracco L, Burghes AH, Bollen M, Stamm S., Protein phosphatase 1 binds to the RNA recognition motif of several splicing factors and regulates alternative pre-mRNA processing. Hum Mol Genet17(1):52-70 2007 |
| PubMed ID: 17913700 |
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| Simard LR, Bélanger MC, Morissette S, Wride M, Prior TW, Swoboda KJ, Preclinical validation of a multiplex real-time assay to quantify SMN mRNA in patients with SMA Neurology68:451-6 2007 |
| PubMed ID: 17283322 |
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| Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, Cizman Z, Di Prospero NA, Pellizzoni L, Fischbeck KH, Sumner CJ, Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy The Journal of clinical investigation117:659-71 2006 |
| PubMed ID: 17318264 |
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| Singh NK, Singh NN, Androphy EJ, Singh RN, Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron Molecular and cellular biology26:1333-46 2006 |
| PubMed ID: 16449646 |
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| Kernochan LE, Russo ML, Woodling NS, Huynh TN, Avila AM, Fischbeck KH, Sumner CJ, The role of histone acetylation in SMN gene expression. Hum Mol Genet14(9):1171-82 2005 |
| PubMed ID: 15772088 |
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| Wan L, Battle DJ, Yong J, Gubitz AK, Kolb SJ, Wang J, Dreyfuss G, The survival of motor neurons protein determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy Molecular and cellular biology25:5543-51 2005 |
| PubMed ID: 15964810 |
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| Kelley BP, Lunn MR, Root DE, Flaherty SP, Martino AM, Stockwell BR, A flexible data analysis tool for chemical genetic screens. Chem Biol11(11):1495-503 2004 |
| PubMed ID: 15556000 |
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| Lunn MR, Root DE, Martino AM, Flaherty SP, Kelley BP, Coovert DD, Burghes AH, Man NT, Morris GE, Zhou J, Androphy EJ, Sumner CJ, Stockwell BR, Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. Chem Biol11(11):1489-93 2004 |
| PubMed ID: 15555999 |
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| DiDonato CJ, Parks RJ, Kothary R, Development of a gene therapy strategy for the restoration of survival motor neuron protein expression: implications for spinal muscular atrophy therapy. Hum Gene Ther14(2):179-88 2003 |
| PubMed ID: 12614569 |
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| Sumner CJ, Huynh TN, Markowitz JA, Perhac JS, Hill B, Coovert DD, Schussler K, Chen X, Jarecki J, Burghes AH, Taylor JP, and Fischbeck KH.
, Valproic acid increases SMN levels in spinal muscular atrophy patient cells.
Ann Neurol54:647-654 2003 |
| PubMed ID: 14595654 |
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| Gangwani L, Mikrut M, Theroux S, Sharma M, Davis RJ, Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein. Nat Cell Biol3(4):376-83 2001 |
| PubMed ID: 11283611 |
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| Scudiero DA, Polinsky RJ, Brumback RA, Tarone RE, Nee LE, Robbins JH, Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical. Mutat Res159:125-31 1986 |
| PubMed ID: 3941662 |
| Passage Frozen |
7 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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