Human laminopathies: nuclei gone genetically awry (original) (raw)

• Gruenbaum, Y., Margalit, A., Goldman, R. D., Shumaker, D. K. & Wilson, K. L. The nuclear lamina comes of age. Nature Rev. Mol. Cell Biol. 6, 21–31 (2005).
  Article CAS Google Scholar
• Lin, F. & Worman, H. J. Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C. J. Biol. Chem. 268, 16321–16326 (1993).
  Article CAS PubMed Google Scholar
• Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J. & Lawrence, J. B. Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. Genomics 32, 474–478 (1996).
  Article CAS PubMed Google Scholar
• Hutchinson, C. J. Lamins: building blocks or regulators of gene expression. Nature Rev. Mol. Cell Biol. 3, 848–858 (2002).
  Article CAS Google Scholar
• Burke, B., Mounkes, L. C. & Stewart, C. L. The nuclear envelope in muscular dystrophy and cardiovascular diseases. Traffic 2, 675–683 (2001).
  Article CAS PubMed Google Scholar
• Beck, L. A., Hosick, T. J. & Sinensky, M. Isoprenylation is required for the processing of the lamin A precursor. J. Cell Biol. 110, 1489–1499 (1990). The first demonstration that farnesylation is required for the processing of prelamin A to lamin A.
  Article CAS PubMed Google Scholar
• Boyartchuk, V. L., Ashby, M. N. & Rine, J. Modulation of ras and a-factor function by carboxyl-terminal proteolysis. Science 275, 1796–1800 (1997).
  Article CAS PubMed Google Scholar
• Sinensky, M. et al. The processing pathway of prelamin A. J. Cell. Sci. 107, 61–67 (1994).
  Article CAS PubMed Google Scholar
• Bergo, M. O. et al. Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect. Proc. Natl Acad. Sci. USA 99, 13049–13054 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Dai, Q. et al. Mammalian prenylcysteine carboxyl methyltransferase is in the endoplasmic reticulum. J. Biol. Chem. 273, 15030–15034 (1998).
  Article CAS PubMed Google Scholar
• Hennekes, H. & Nigg, E. A. The role of isoprenylation in membrane attachment of nuclear lamins. J. Cell Sci. 107, 1019–1029 (1994).
  Article CAS PubMed Google Scholar
• Vergnes, L., Peterfy, M., Bergo, M. O., Young, S. G. & Reue, K. Lamin B1 is required for mouse development and nuclear integrity. Proc. Natl Acad. Sci. USA 101, 10428–10433 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Constantinescu, D., Gray, H. L., Sammak, P. J., Schatten, G. P. & Csoka, A. B. Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells 24, 177–185 (2006).
  Article CAS PubMed Google Scholar
• DeBusk, F. L. The Hutchinson–Gilford progeria syndrome. J. Pediatr. 80, 697–724 (1972).
  Article CAS PubMed Google Scholar
• Sarkar, P. K., Shinton, R. A. Hutchinson–Gilford progeria syndrome. Postgrad. Med. J. 77, 312–217 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Baker, P. B., Baba, N. & Boesel, C. P. Cardiovascular abnormalities in progeria. Case report and review of the literature. Arch. Pathol. Lab. Med. 105, 384–386 (1981).
  CAS PubMed Google Scholar
• Hutchinson, J. Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages in a boy whose mother had been almost totally bald from alopecia areata from the age of six. Medicochir. Trans. 69, 473–477 (1886).
  CAS Google Scholar
• Eriksson, M. et al. Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome. Nature 423, 293–298 (2003). The seminal paper that identified and characterized the G608G LMNA mutation as the cause of approximately 90% of HGPS cases. This paper described the 50-amino-acid preterminal deletion and noted the presence of blebbed nuclei in HGPS.
  Article CAS PubMed Google Scholar
• De Sandre-Giovannoli, A. et al. Lamin A truncation in Hutchinson–Gilford progeria. Science 300, 2055 (2003).
  Article CAS PubMed Google Scholar
• D'Apice, M. R., Tenconi, R., Mammi, I., van den Ende, J. & Novelli, G. Paternal origin of LMNA mutations in Hutchinson–Gilford progeria syndrome. Clin. Genet. 65, 52–54 (2004).
  Article CAS PubMed Google Scholar
• Capell, B. C. et al. Inhibiting the farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson–Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 102, 12879–12884 (2005). Demonstrated the in vitro efficacy of the clinical candidate FTI lonafarnib to prevent the nuclear blebbing that is seen in human HGPS fibroblasts, as well as providing evidence to suggest that progerin is not alternatively geranylgeranylated when farnesylation is inhibited.
  Article CAS Google Scholar
• Yang, S. H. et al. Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson–Gilford progeria syndrome mutation. Proc. Natl Acad. Sci. USA 102, 10291–10296 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Toth, J. I. et al. Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc. Natl Acad. Sci. USA 102, 12873–12878 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Glynn, M. W. & Glover, T. W. Incomplete processing of mutant lamin A in Hutchinson–Gilford progeria syndrome leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition. Hum. Mol. Genet. 14, 2959–2969 (2005).
  Article CAS PubMed Google Scholar
• Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H. & Michaelis, S. Inhibiting farnesylation reverses the nuclear morphology defect in a HeLa cell model for Hutchinson–Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 102, 14416–14421 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Reddel, C. J. & Weiss, A. S. Lamin A expression levels are unperturbed at the normal and mutant alleles but display partial splice site selection in Hutchinson–Gilford progeria syndrome. J. Med. Genet. 41, 715–717 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Goldman, R. D. et al. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson–Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 101, 8963–8968 (2004). The first description of the passage-dependent nuclear blebbing, loss of peripheral heterochromatin and nuclear pore clustering that is seen in HGPS cells.
  Article CAS PubMed PubMed Central Google Scholar
• Scaffidi, P. & Misteli, T. Reversal of the cellular phenotype in the premature aging disease Hutchinson–Gilford progeria syndrome. Nature Med. 11, 440–445 (2005). The first demonstration of the reversal of the nuclear phenotype of HGPS using a modified oligonucleotide that is targeted to the activated lamin A cryptic splice site used in HGPS.
  Article CAS PubMed Google Scholar
• Csoka, A. B. et al. Genome-scale expression profiling of Hutchinson–Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell 4, 235–243 (2004).
  Article CAS Google Scholar
• Delbarre, E. et al. The truncated prelamin A in Hutchinson–Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers. Hum. Mol. Genet. 15, 1113–1122 (2006).
  Article CAS PubMed Google Scholar
• Paradisi, M. et al. Dermal fibroblasts in Hutchinson–Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress. BMC Cell Biol. 6, 27 (2005).
  Article PubMed PubMed Central CAS Google Scholar
• Shumaker, D. K. et al. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc. Natl Acad. Sci. USA 103, 8703–8708 (2006). The first paper to show that, prior to nuclear blebbing, HGPS cells undergo broad and dramatic epigenetic changes that might contribute to the rapid premature ageing that is seen in HGPS patients.
  Article CAS PubMed PubMed Central Google Scholar
• McClintock, D., Gordon, L. B. & Djabali, K. Hutchinson–Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. Proc. Natl Acad. Sci. USA 103, 2154–2159 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Yu, C. E. et al. Positional cloning of the Werner's syndrome gene. Science 272, 258–262 (1996).
  Article CAS PubMed Google Scholar
• Chen, L. et al. LMNA mutations in atypical Werner's syndrome. Lancet 362, 440–445 (2003).
  Article CAS PubMed Google Scholar
• Adelfalk, C., Scherthan, H., Hirsch-Kauffmann, M. & Schweiger, M. Nuclear deformation characterizes Werner syndrome cells. Cell Biol. Int. 29, 1032–1037 (2005).
  Article CAS PubMed Google Scholar
• Csoka, A. B. et al. Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J. Med. Genet. 41, 304–308 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Caux, F. et al. A new clinical condition linked to a novel condition in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J. Clin. Endocrinol. Metab. 88, 1006–1013 (2003).
  Article CAS PubMed Google Scholar
• Bione, S. et al. Identification of a novel X-linked gene responsible for Emery–Dreifuss muscular dystrophy. Nature Genet. 8, 323–327 (1994).
  Article CAS PubMed Google Scholar
• Bonne, G. et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery–Dreifuss muscular dystrophy. Nature Genet. 21, 285–288 (1999).
  Article CAS PubMed Google Scholar
• Raffaele di Barletta, M. et al. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery–Dreifuss muscular dystrophy. Am. J. Hum. Genet. 66, 1407–1412 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Manilal, S. et al. Mutations in Emery–Dreifuss muscular dystrophy and their effects on emerin protein expression. Hum. Mol. Genet. 7, 855–864 (1998).
  Article CAS PubMed Google Scholar
• Yates, J. R. & Wehnert, M. The Emery–Dreifuss muscular dystrophy mutation database. Neuromuscul. Disord. 9, 199 (1999).
  Article CAS PubMed Google Scholar
• Brown, C. A et al. Novel and recurrent mutations in lamin A/C in patients with Emery–Dreifuss muscular dystrophy. Am. J. Hum. Genet. 102, 359–367 (2001).
  Article CAS Google Scholar
• Muchir, A. et al. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum. Mol. Genet. 9, 1453–1459 (2000).
  Article CAS PubMed Google Scholar
• Jacob, K. N. & Garg, A. Laminopathies: multisystem dystrophy syndromes. Mol. Genet. Metab. 87, 289–302 (2006).
  Article CAS PubMed Google Scholar
• Todorova, A. et al. A synonymous codon change in the LMNA gene alters mRNA splicing and causes limb girdle muscular dystrophy type 1B. J. Med. Genet. 40, e115 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Fatkin, D. et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N. Engl. J. Med. 341, 1715–1724 (1999).
  Article CAS PubMed Google Scholar
• Brodsky, G. L. et al. Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation 101, 473–476 (2000).
  Article CAS PubMed Google Scholar
• De Sandre-Giovannoli, A. et al. Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot–Marie–Tooth disorder type 2) and mouse. Am. J. Hum. Genet. 70, 726–736 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Tazir, M. et al. Phenotype variability in autosomal recessive axonal Charcot–Marie–Tooth disease due to the R298C mutation in lamin A/C. Brain 127, 154–163 (2003).
  Article PubMed Google Scholar
• Cao, H. & Hegele, R. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum. Mol. Genet. 9, 109–112 (2000).
  Article CAS PubMed Google Scholar
• Shackleton, S. et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nature Genet. 24, 153–156 (2000).
  Article CAS PubMed Google Scholar
• Speckman, R. A. et al. Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C. Am. J. Hum. Genet. 66, 1192–1198 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Dhe-Paganon, S., Werner, E. D., Chi, Y. & Shoelson, S. E. Structure of the globular tail of nuclear lamin. J. Biol. Chem. 277, 17381–17384 (2002).
  Article CAS PubMed Google Scholar
• Krimm, I. et al. The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies, cardiomyopathy, and partial lipodystrophy. Structure 10, 811–823 (2002).
  Article CAS PubMed Google Scholar
• Novelli, G. et al. Mandibuloacral dysplasia is caused by a mutation in _LMNA_-encoding lamin A/C. Am. J. Hum. Genet. 71, 426–431 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Agarwal, A. K., Fryns, J. P., Auchus, R. J. & Garg, A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum. Mol. Genet. 12, 1995–2001 (2003).
  Article CAS PubMed Google Scholar
• Filesi, I. et al. Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy. Physiol. Genomics 23, 150–158 (2005).
  Article CAS PubMed Google Scholar
• Navarro, C. L. et al. Lamin A and ZMPSTE24 (FACE1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum. Mol. Genet. 13, 2493–2503 (2004).
  Article CAS PubMed Google Scholar
• Navarro, C. L. et al. Loss of ZMPSTE24 (FACE1) causes autosomal recessive restrictive dermopathy and accumulation of lamin A precursors. Hum. Mol. Genet. 14, 1503–1513 (2005).
  Article CAS PubMed Google Scholar
• Moulson, C. L. et al. Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy. J. Invest. Dermatol. 125, 913–919 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Kirschner, J. et al. p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria. Ann. Neurol. 57, 148–151 (2004).
  Article CAS Google Scholar
• Goizet, C. et al. A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J. Med. Genet. 41, e29 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Van Esch, H., Agarwal, A. K., Debeer, P., Fryns, J. P. & Garg, A. A homozygous mutation in the lamin A/C gene associated with a novel syndrome of arthropathy, tendinous calcinosis, and progeroid features. J. Clin. Endocrinol. Metab. 91, 517–521 (2006).
  Article CAS PubMed Google Scholar
• Young, J. et al. Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes 54, 1873–1878 (2005).
  Article CAS PubMed Google Scholar
• Hegele, R. A. et al. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am. J. Hum. Genet. 79, 383–389 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Padiath, Q. S. et al. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nature Genet. 38, 1114–1123 (2006). The first demonstration that mutations in LMNB1 can cause human disease.
  Article CAS PubMed Google Scholar
• Waterham, H. R. et al. Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3β-hydroxysterol delta14-reductase deficiency due to mutations in the lamin B receptor gene. Am. J. Hum. Genet. 72, 1013–1017 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Oosterwijk, J. C. et al. Congenital abnormalities reported in Pelger-Huet homozygosity as compared to Greenberg/HEM dysplasia: highly variable expression of allelic phenotypes. J. Med. Genet. 40, 937–941 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Benedetti, S. & Merlini, L. Laminopathies: from the heart of the cell to the clinics. Curr. Opin. Neurol. 17, 553–560 (2004).
  Article CAS PubMed Google Scholar
• Ostlund, C. & Worman, H. J. Nuclear envelope proteins and neuromuscular disease. Muscle Nerve 27, 393–406 (2003).
  Article CAS PubMed Google Scholar
• Dahl, K. N., Kahn, S. M., Wilson, K. L. & Discher, D. E. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J. Cell Sci. 117, 4779–4786 (2004).
  Article CAS PubMed Google Scholar
• Sullivan, T. et al. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147, 913–920 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Lammerding, J. et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113, 370–378 (2004). Demonstrated the mechanical role of A-type lamins in nuclear stability, and how perturbing an abnormal lamina with mechanical strain can affect downstream transcription.
  Article CAS PubMed PubMed Central Google Scholar
• Broers, J. L. et al. Decreased mechanical stiffness in LMNA−/− cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies. Hum. Mol. Genet. 13, 2567–2580 (2004).
  Article CAS PubMed Google Scholar
• Nikolova, V. et al. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. J. Clin. Invest. 113, 357–369 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Glass, C. A. et al. The α-helical rod domain of human lamins A and C contains a chromatin binding site. EMBO J. 12, 4413–4424 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Taniura, H., Glass, C. & Gerace, L. A chromatin binding site in the tail domain of nuclear lamins that interacts with core histones. J. Cell Biol. 131, 33–44 (1995).
  Article CAS PubMed Google Scholar
• Pickersgill, H. et al. Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nature Genet. 38, 1005–1014 (2006). Provided the first in vivo evidence for the dynamic role of the lamina in genomic organization and expression.
  Article CAS PubMed Google Scholar
• Capanni, C. et al. Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered intermolecular interaction with emerin and implications for gene transcription. Exp. Cell Res. 291, 122–134 (2003).
  Article CAS PubMed Google Scholar
• Spann, T. P., Moir, R. D., Goldman, A. E., Stick, R. & Goldman, R. Disruption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis. J. Cell Biol. 136, 1201–1212 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Jagatheesan, G. et al. Colocalization of intranuclear lamin foci with RNA splicing factors. J. Cell Sci. 112, 4651–4661 (1999).
  Article CAS PubMed Google Scholar
• Ivorra, C. et al. A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev. 20, 307–320 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Lloyd, D. J., Trembath, R. C. & Shackleton, S. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum. Mol. Genet. 11, 769–777 (2002).
  Article CAS PubMed Google Scholar
• Broers, J. L., Hutchinson, C. J. & Ramaekers, F. C. Laminopathies. J. Pathol. 204, 478–488 (2004).
  Article CAS PubMed Google Scholar
• Bengtsson, L. & Wilson, K. L. Barrier-to-autointegration factor phosphorylation on Ser-4 regulates emerin binding to lamin A in vitro and emerin localization in vivo. Mol. Biol. Cell 17, 1154–1163 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Melcon, G. et al. Loss of emerin at the nuclear envelope disrupts the Rb/E2F and MyoD pathways during muscle regeneration. Hum. Mol. Genet. 15, 637–651 (2006).
  Article CAS PubMed Google Scholar
• Flemington, E. K., Speck, S. H. & Kaelin, W. G. E2F1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. Proc. Natl Acad. Sci. USA 90, 6914–6918 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Johnson, B. R. et al. A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc. Natl Acad. Sci. USA 101, 19677–19682 (2004).
  Google Scholar
• Frock, R. L. et al. Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev. 20, 486–500 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Van Berlo, J. H. et al. A-type lamins are essential for TGFβ1 induced PP2A to dephosphorylate transcription factors. Hum. Mol. Genet. 14, 2839–2849 (2005).
  Article CAS PubMed Google Scholar
• Mounkes, L. C., Kozlov, S., Hernandez, L., Sullivan, T. & Stewart, C. L. A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 423, 298–301 (2003).
  Article CAS PubMed Google Scholar
• Boguslavsky, R. L., Stewart, C. L. & Worman, H. J. Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy. Hum. Mol. Genet. 15, 653–663 (2006).
  Article CAS PubMed Google Scholar
• Capanni, C. et al. Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum. Mol. Genet. 14, 1489–1502 (2005).
  Article CAS PubMed Google Scholar
• Tsai, M. et al. A mitotic lamin B matrix induced by RanGTP required for spindle assembly. Science 311, 1187–1893 (2006). The first proof of the role of the lamina in mitosis, in particular the essential role of lamin B in the formation of the mitotic matrix that assists in spindle assembly.
  Article CAS Google Scholar
• Zastrow, M. S., Flaherty, D. B., Benian, G. M. & Wilson, K. L. Nuclear titin interacts with A- and B-type lamins in vitro and in vivo. J. Cell Sci. 119, 239–249 (2006).
  Article CAS PubMed Google Scholar
• Lans, H. & Hoeijmakers, J. H. Ageing nucleus gets out of shape. Nature 440, 32–34 (2006).
  Article CAS PubMed Google Scholar
• Scaffidi, P., Gordon, L. & Misteli, T. The cell nucleus and aging: tantalizing clues and hopeful promises. PLoS Biol. 3, 1855–1859 (2006).
  Google Scholar
• Pendas, A. M. et al. Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice. Nature Genet. 31, 94–99 (2002).
  Article CAS PubMed Google Scholar
• Liu, B. et al. Genomic instability in laminopathy-based premature aging. Nature Med. 11, 780–785 (2005). Demonstrated the potential relationship between DNA damage, chromosomal aberrations, genome instability and premature ageing in both a HGPS mouse model and HGPS fibroblasts.
  Article CAS PubMed Google Scholar
• Varela, I. et al. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437, 564–566 (2005).
  Article CAS PubMed Google Scholar
• Fong, L. G. et al. Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in _Zmpste24_-deficient mice. Proc. Natl Acad. Sci. USA 101, 18111–18116 (2004). Provided in vivo proof that reducing the level of farnesylated prelamin A by half can dramatically ameliorate a severe phenotype in a progeria mouse model.
  Article CAS PubMed PubMed Central Google Scholar
• Fong, L. G. et al. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J. Clin. Invest. 116, 743–752 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Basso, A. D., Kirschmeier, P. & Bishop, W. R. Farnesyl transferase inhibitors. J. Lipid Res. 47, 15–31 (2006).
  Article CAS PubMed Google Scholar
• Fong, L. G. et al. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 311, 1621–1623 (2006). The first in vivo demonstration of the efficacy of farnesyltransferase inhibitors in a progeria mouse model.
  Article CAS PubMed Google Scholar
• Yang, S. H. et al. A farnesyltransferase inhibitor improves disease phenotype in mice with a Hutchinson–Gilford progeria syndrome mutation. J. Clin. Invest. 116, 2115–2121 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Sebti, S. M. & Der, C. J. Searching for the elusive targets of farnesyltransferase inhibitors. Nature Rev. Cancer 3, 945–951 (2003).
  Article CAS Google Scholar
• Efuet, E. T. & Keyomarsi, K. Farnesyl and geranylgeranyl transferase inhibitors induce G1 arrest by targeting the proteasome. Cancer Res. 66, 1040–1051 (2006).
  Article CAS PubMed Google Scholar
• Doll, R. J., Kirschmeier, P. & Bishop, W. R. Farneyltransferase inhibitors as anticancer agents: critical crossroads. Curr. Opin. Drug Discov. Devel. 7, 478–486 (2004).
  CAS PubMed Google Scholar
• Winter-Vann, A. M. & Casey, P. J. Post-prenylation-processing enzymes as new targets in oncogenesis. Nature Rev. Cancer 5, 405–412 (2005).
  Article CAS Google Scholar
• Demierre, M., Higgins, P. D. R., Gruber, S. B., Hawk, E. & Lippman, S. M. Statins and cancer prevention. Nature Rev. Cancer 5, 930–942 (2005).
  Article CAS Google Scholar
• Columbaro, M. et al. Rescue of heterochromatin organization in Hutchinson–Gilford progeria by drug treatment. Cell. Mol. Life Sci. 62, 2669–2678 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Huang, S. et al. Correction of cellular phenotypes of Hutchinson–Gilford progeria cells by RNA interference. Hum. Genet. 118, 444–450 (2005).
  Article CAS PubMed Google Scholar
• Zimmermann, T. S. et al. RNAi-mediated gene silencing in non-human primates. Nature 441, 111–114 (2006).
  Article CAS PubMed Google Scholar
• Sazani, P. & Kole, R. Therapeutic potential of antisense oligonucleotides as modulators of alternative splicing. J. Clin. Invest. 112, 481–486 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Scaffidi, P. & Misteli, T. Lamin A-dependent nuclear defects in human aging. Science 312, 1059–1063 (2006). The first evidence for nuclear phenotypic similarities between aged fibroblasts and HGPS fibroblasts. Also showed that normal cells use the same cryptic splice site that is used in HGPS and produce small amounts of the mutant progerin protein.
  Article CAS PubMed PubMed Central Google Scholar
• Haithcock, E. et al. Age-related changes of nuclear architecture in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 102, 16690–16695 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Hegele, R. A. & Pollex, R. L. Genetic and physiological insights into the metabolic syndrome. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R663–R669 (2005).
  Article CAS PubMed Google Scholar
• Stehbens, W. E., Wakefield, S. J., Gilbert-Barness, E., Olson, R. E. & Ackerman, J. Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc. Pathol. 8, 29–39 (1999).
  Article CAS PubMed Google Scholar
• Stehbens, W. E., Delahunt, B., Shozawa, T. & Gilbert-Barness, E. Smooth muscle cell depletion and collagen types in progeric arteries. Cardiovasc. Pathol. 10, 133–136 (2001).
  Article CAS PubMed Google Scholar
• Varga, R. et al. Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson–Gilford progeria syndrome. Proc. Natl Acad. Sci. USA 103, 3250–3255 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Gordon, L. B., Harten, I. A., Patti, M. E. & Lichtenstein, A. H. Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: clues to the biology of premature atherosclerosis in Hutchinson–Gilford Progeria Syndrome. J. Pediatr. 146, 336–341 (2005).
  Article CAS PubMed Google Scholar
• Low, A. F. et al. Aging syndrome genes and premature coronary artery disease. BMC Med. Genet. 6, 38 (2005).
  Article PubMed PubMed Central CAS Google Scholar
• Mounkes, L. C., Kozlov, S. V., Rottman, J. N. & Stewart, C. L. Expression of an _LMNA_-N195K variant of A-type lamins results in cardiac conduction defects and death in mice. Hum. Mol. Genet. 14, 2167–2180 (2005).
  Article CAS PubMed Google Scholar
• Arimura, T., et al. Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum. Mol. Genet. 14, 155–169 (2005).
  Article CAS PubMed Google Scholar
• Mason, J. C. et al. Statins and their role in vascular protection. Clin. Sci. (Lond.) 105, 251–266 (2003).
  Article CAS Google Scholar