AG11513
Fibroblast from Skin, Leg
Description:
HUTCHINSON-GILFORD PROGERIA SYNDROME; HGPS
LAMIN A/C; LMNA
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Repository
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NIA Aging Cell Culture Repository
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| Subcollection |
Heritable Diseases |
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Biopsy Source
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Leg
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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, Leg
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Race
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White
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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 |
4.89 |
| Passage Frozen |
10 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
LMNA |
| Chromosomal Location |
1q21.2 |
| Allelic Variant 1 |
150330.0022; HUTCHINSON-GILFORD PROGERIA SYNDROME |
| Identified Mutation |
GLY608GLY; Description: In 18 of 20 patients with classic Hutchinson-Gilford progeria syndrome (176670), Eriksson et al. [Nature 423: 293 (2003)] found an identical de novo single-base substitution, a C-to-T change resulting in a silent gly-to-gly mutation at codon 608 (G608G) within exon 11 of the LMNA gene. This substitution created an exonic consensus splice donor sequence and resulted in activation of a cryptic splice site and deletion of 50 basepairs of prelamin A. This mutation was not identified in any of the 16 parents available for testing. |
| Remarks |
Donor showed typical appearance including alopecia and bilateral symmetrical coxa valga. The biopsy was taken ante-mortem on 5/09/91 from skin of the anterior upper leg. The culture was initiated on 5/10/91 using explants of minced skin tissue. The cell morphology is fibroblast-like. Donor subject has a de novo single base substitution, a C>T change at nucleotide 2036 (2036C>T), which results in a silent change at codon 608 [Gly608Gly (G608G)] in exon 11 of the Lamin A gene (LMNA). This substitution creates an exonic consensus splice donor sequence and results in activation of a cryptic splice site which in turn causes skipping of 150 bp of the LMNA mRNA leading to the deletion of 50 amino acids from the protein. This altered LMNA protein was detected on western blots [Eriksson et al., Nature 423:293 (2003)]. |
| Catarinella G, Nicoletti C, Bracaglia A, Procopio P, Salvatori I, Taggi M, Valle C, Ferri A, Canipari R, Puri PL, Latella L, SerpinE1 drives a cell-autonomous pathogenic signaling in Hutchinson-Gilford progeria syndrome Cell death & disease13:737 2022 |
| PubMed ID: 36028501 |
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| Frankel D, Delecourt V, Novoa-Del-Toro EM, Robin JD, Airault C, Bartoli C, Carabalona A, Perrin S, Mazaleyrat K, De Sandre-Giovannoli A, Magdinier F, Baudot A, Lévy N, Kaspi E, Roll P, miR-376a-3p and miR-376b-3p overexpression in Hutchinson-Gilford progeria fibroblasts inhibits cell proliferation and induces premature senescence iScience25:103757 2021 |
| PubMed ID: 35118365 |
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| Kychygina A, Dall'Osto M, Allen JAM, Cadoret JC, Piras V, Pickett HA, Crabbe L, Progerin impairs 3D genome organization and induces fragile telomeres by limiting the dNTP pools Scientific reports11:13195 2021 |
| PubMed ID: 34162976 |
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| Arii J, Maeda F, Maruzuru Y, Koyanagi N, Kato A, Mori Y, Kawaguchi Y, ESCRT-III controls nuclear envelope deformation induced by progerin Scientific reports10:18877 2020 |
| PubMed ID: 33139753 |
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| Kang SM, Yoon MH, Ahn J, Kim JE, Kim SY, Kang SY, Joo J, Park S, Cho JH, Woo TG, Oh AY, Chung KJ, An SY, Hwang TS, Lee SY, Kim JS, Ha NC, Song GY, Park BJ, Progerinin, an optimized progerin-lamin A binding inhibitor, ameliorates premature senescence phenotypes of Hutchinson-Gilford progeria syndrome Communications biology4:5 2020 |
| PubMed ID: 33398110 |
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| Lee J, Bignone PA, Coles LS, Liu Y, Snyder E, Larocca D, Induced pluripotency and spontaneous reversal of cellular aging in supercentenarian donor cells Biochemical and biophysical research communications4:5 2020 |
| PubMed ID: 32115145 |
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| Chen WM, Chiang JC, Lin YC, Lin YN, Chuang PY, Chang YC, Chen CC, Wu KY, Hsieh JC, Chen SK, Huang WP, Chen BPC, Lee H, Lysophosphatidic acid receptor LPA Aging cell4:e13064 2019 |
| PubMed ID: 31714004 |
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| Fan JR, You LR, Wang WJ, Huang WS, Chu CT, Chi YH, Chen HC, Lamin A-mediated nuclear lamina integrity is required for proper ciliogenesis EMBO reports4:e49680 2019 |
| PubMed ID: 32815283 |
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| Lan YY, Heather JM, Eisenhaure T, Garris CS, Lieb D, Raychowdhury R, Hacohen N, Extranuclear DNA accumulates in aged cells and contributes to senescence and inflammation Aging cell4:e12901 2018 |
| PubMed ID: 30706626 |
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| Larrieu D1, Viré E2, Robson S2, Breusegem SY2, Kouzarides T2, Jackson SP1., Inhibition of the acetyltransferase NAT10 normalizes progeric and aging cells by rebalancing the Transportin-1 nuclear import pathway Science Signaling11:e12901 2018 |
| PubMed ID: 29970603 |
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| Li Y, Zhou G, Bruno IG, Zhang N, Sho S, Tedone E, Lai TP, Cooke JP, Shay JW, Transient introduction of human telomerase mRNA improves hallmarks of progeria cells Aging cell18:e12979 2018 |
| PubMed ID: 31152494 |
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| Chen CY, Chi YH, Mutalif RA, Starost MF, Myers TG, Anderson SA, Stewart CL, Jeang KT., Accumulation of inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell149:565-77 2012 |
| PubMed ID: 22541428 |
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| Nissan X, Blondel S, Navarro C, Maury Y, Denis C, Girard M, Martinat C, De Sandre-Giovannoli A, Levy N, Peschanski M, Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA Cell reports2:1-9 2011 |
| PubMed ID: 22840390 |
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| Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Löbrich M, Jeggo PA, ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin Molecular cell31:167-77 2007 |
| PubMed ID: 18657500 |
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| Moulson CL, Fong LG, Gardner JM, Farber EA, Go G, Passariello A, Grange DK, Young SG, Miner JH, Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes Human mutation28:882-9 2007 |
| PubMed ID: 17469202 |
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| Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y, DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A Journal of cell science119:4644-9 2006 |
| PubMed ID: 17062639 |
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| Capell BC, Erdos MR, Madigan JP, Fiordalisi JJ, Varga R, Conneely KN, Gordon LB, Der CJ, Cox AD, Collins FS, Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome Proceedings of the National Academy of Sciences of the United States of America102:12879-84 2005 |
| PubMed ID: 16129833 |
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| Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL, Miner JH, Young SG, Fong LG, Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes Proceedings of the National Academy of Sciences of the United States of America102:12873-8 2005 |
| PubMed ID: 16129834 |
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| Csoka AB, English SB, Simkevich CP, Ginzinger DG, Butte AJ, Schatten GP, Rothman FG, Sedivy JM, Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell3(4):235-43 2004 |
| PubMed ID: 15268757 |
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| Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, Gruenbaum Y, Khuon S, Mendez M, Varga R, Collins FS, Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A101(24):8963-8 2004 |
| PubMed ID: 15184648 |
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| Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS, Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature423(6937):293-8 2003 |
| PubMed ID: 12714972 |
| Passage Frozen |
10 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
3% |
| Medium |
Eagles Minimum Essential Medium with Earle's salts:Dulbecco's modified MEM with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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