AG01972
Fibroblast from Skin, Thorax
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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Thorax
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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, Thorax
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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 |
5 |
| Passage Frozen |
12 |
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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 and by Chromosome Analysis |
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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 classic features of progeria. The biopsy was taken antemortem on 2/14/75 from skin of the thorax area. The culture was initiated using explants of minced skin tissue. The cell morphology is fibroblastlike. The karyotype is 46,XX; normal diploid female with 6% of cells examined showing random chromosome loss. 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)]. The legacy karyotype description shown in this Remark may not be representative of the current available product. |
| Li M, Zhong A, Wu Y, Sidharta M, Beaury M, Zhao X, Studer L, Zhou T, Transient inhibition of p53 enhances prime editing and cytosine base-editing efficiencies in human pluripotent stem cells Nature communications13:6354 2022 |
| PubMed ID: 36302757 |
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| Jühlen R, Martinelli V, Vinci C, Breckpot J, Fahrenkrog B, Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts Scientific reports10:19301 2020 |
| PubMed ID: 33168876 |
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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 communications10:19301 2020 |
| PubMed ID: 32115145 |
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| Clements CS, Bikkul MU, Ofosu W, Eskiw C, Tree D, Makarov E, Kill IR, Bridger JM, Presence and distribution of progerin in HGPS cells is ameliorated by drugs that impact on the mevalonate and mTOR pathways Biogerontology20:337-358 2019 |
| PubMed ID: 31041622 |
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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 reports20:e49680 2019 |
| PubMed ID: 32815283 |
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| Bikkul MU1, Clements CS1, Godwin LS1, Goldberg MW2, Kill IR1, Bridger JM, Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson-Gilford progeria syndrome fibroblasts Biogerontology20:e49680 2018 |
| PubMed ID: 29907918 |
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| Dworak N, Makosa D, Chatterjee M, Jividen K, Yang CS, Snow C, Simke WC, Johnson IG, Kelley JB, Paschal BM, A nuclear lamina-chromatin-Ran GTPase axis modulates nuclear import and DNA damage signaling Aging Cell20:e49680 2018 |
| PubMed ID: 30565836 |
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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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| Barcena C, Osorio FG, Freije JM, Detection of nuclear envelope alterations in senescence Methods Mol Biol965:243-51 2013 |
| PubMed ID: 23296663 |
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| Kane MS, Lindsay ME, Judge DP, Barrowman J, Ap Rhys C, Simonson L, Dietz HC, Michaelis S, LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset Am J Med Genet A161A(7):1599-611 2013 |
| PubMed ID: 23666920 |
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| Rivera-Torres J, Acín-Perez R, Cabezas-Sánchez P, Osorio FG, Gonzalez-Gómez C, Megias D, Cámara C, López-Otín C, Enríquez JA, Luque-García JL, Andrés V., Identification of mitochondrial dysfunction in Hutchinson-Gilford progeria syndrome through use of stable isotope labeling with amino acids in cell culture. J Proteomics.91C:466-477 2013 |
| PubMed ID: 23969228 |
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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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| Ragnauth CD, Warren DT, Liu Y, McNair R, Tajsic T, Figg N, Shroff R, Skepper J, Shanahan CM, Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging Circulation121:2200-10 2010 |
| PubMed ID: 20458013 |
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| Cao K, Capell BC, Erdos MR, Djabali K, Collins FS, A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells Proceedings of the National Academy of Sciences of the United States of America104:4949-54 2007 |
| PubMed ID: 17360355 |
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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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| Scaffidi P, Misteli T, Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing Nature cell biology28:882-9 2007 |
| PubMed ID: 18311132 |
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| Huang S, Chen L, Libina N, Janes J, Martin GM, Campisi J, Oshima J, Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference Human genetics118:444-50 2005 |
| PubMed ID: 16208517 |
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| Scaffidi P, Misteli T, Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med11(4):440-5 2005 |
| PubMed ID: 15750600 |
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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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| 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 |
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| Guernsey DL, Koebbe M, Thomas JE, Myerly TK, Zmolek D, An altered response in the induction of cell membrane (Na + K)ATPase by thyroid hormone is characteristic of senescence in cultured human fibroblasts. Mech Ageing Dev33:283-93 1986 |
| PubMed ID: 3012221 |
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| Conover CA, Dollar LA, Rosenfeld RG, Hintz RL, Somatomedin C-binding and action in fibroblasts from aged and progeric subjects. J Clin Endocrinol Metab60:685-91 1985 |
| PubMed ID: 2579088 |
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| Weichselbaum RR, Nove J, Little JB, X-ray sensitivity of fifty-three human diploid fibroblast cell strains from patients with characterized genetic disorders. Cancer Res40:920-5 1980 |
| PubMed ID: 7471105 |
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| Martin GM, Sprague CA, Epstein CJ, Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype. Lab Invest23:86-92 1970 |
| PubMed ID: 5431223 |
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| Martin GM, Sprague CA, Epstein CJ, Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype. Lab Invest23:86-92 1970 |
| PubMed ID: 29931650 |
| Passage Frozen |
12 |
| 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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