Repository NIA Aging Cell Culture Repository
Subcollection Heritable Diseases
Biopsy Source Thorax
Cell Type Fibroblast
Tissue Type Skin
Transformant Untransformed
Race Caucasian
Relation to Proband proband
Confirmation Clinical summary/Case history
Species Homo sapiens
Common Name Human
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)].
PDL at Freeze 6.12
Passage Frozen 16
 
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
 
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.
Remark 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)].
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 Biogerontology: 2018
PubMed ID: 29907918
 
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 Cell: 2018
PubMed ID: 30565836
 
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
 
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
 
Barcena C, Osorio FG, Freije JM, Detection of nuclear envelope alterations in senescence Methods Mol Biol965:243-51 2013
PubMed ID: 23296663
 
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
 
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
 
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
 
Scaffidi P, Misteli T, Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing Nature cell biology121:2200-10 2007
PubMed ID: 18311132
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
No data is available
Cumulative PDL at Freeze 38.1
Passage Frozen 16
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
Serum 15% fetal bovine serum Not inactivated