Skip to main content
PMC home page
Cellular & Molecular Biology Letters logoLink to Cellular & Molecular Biology Letters
. 2010 Dec 27;16(1):114–148. doi: 10.2478/s11658-010-0038-9

Laminopathies: The molecular background of the disease and the prospects for its treatment

Magdalena Zaremba-Czogalla 1, Magda Dubińska-Magiera 1, Ryszard Rzepecki 1,✉
PMCID: PMC6275778  PMID: 21225470

Abstract

Laminopathies are rare human degenerative disorders with a wide spectrum of clinical phenotypes, associated with defects in the main protein components of the nuclear envelope, mostly in the lamins. They include systemic disorders and tissue-restricted diseases. Scientists have been trying to explain the pathogenesis of laminopathies and find an efficient method for treatment for many years. In this review, we discuss the current state of knowledge about laminopathies, the molecular mechanisms behind the development of particular phenotypes, and the prospects for stem cell and/or gene therapy treatments.

Key words: Laminopathies, Nuclear lamina, Lamin, Emerin, Gene therapy

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Abbreviations used

ADLD

adult-onset autosomal dominant leukodystrophy

APL

acquired partial lipodystrophy

CMD1A

dilated cardiomyopathy 1A with conduction defect

CMT2B1

Charcot-Marie-Tooth disease type 2B1

DMD

Duchenne muscular dystrophy

EDMD

autosomal dominant Emery-Dreifuss muscular dystrophy

ERK

extracellular signal-regulated kinase

GL

generalized lipodystrophy

FPLD

Dunnigan familial partial lipodystrophy

HGPS

Hutchinson Gilford progeria syndrome

INM

inner nuclear membrane

JNK

c-Jun NH(2)-terminal kinase

LAP

lamina-associated polypeptide

LBR

p58 protein, lamin B receptor, 3 beta-hydroxysterol D14-reductase

LGMDB1

limb-girdle muscular dystrophy type 1B

LINC

linker of the nucleoskeleton and cytoskeleton

LMNA

gene encoding A/C type lamins

MAD

mandibuloacral dysplasia

NE

nuclear envelope

PPARγ

peroxisome proliferator-activated receptor γ

pRB

retinoblastoma protein

ZMPSTE24/FACE1

zinc metalloproteinase STE 24 homology

References

  • 1.Worman H.J., Fong L.G., Muchir A., Young S.G. Laminopathies and the long strange trip from basic cell biology to therapy. J. Clin. Invest. 2009;119:1825–1836. doi: 10.1172/JCI37679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Worman H.J., Fong L.G., Muchir A., Young S.G. The nuclear envelope from basic biology to therapy. Biochem. Soc. Trans. 2010;38:253–256. doi: 10.1042/BST0380253. [DOI] [PubMed] [Google Scholar]
  • 3.Foster C.R., Przyborski S.A., Wilson R.G., Hutchison C.J. Lamins as cancer biomarkers. Biochem. Soc. Trans. 2010;38:297–300. doi: 10.1042/BST0380297. [DOI] [PubMed] [Google Scholar]
  • 4.Hetzer, M.W. The Nuclear Envelope. Cold Spring Harb. Perspect Biol. (2010) cshperspect.a000539. [DOI] [PMC free article] [PubMed]
  • 5.Rzepecki R., Smithe C., Hutchison C.J. The role of mitotic vesicles in the nuclear assembly. Cell. Mol. Biol. Lett. 2002;7:299. [PubMed] [Google Scholar]
  • 6.Herrmann H., Bar H., Kreplak L., Strelkov S.V., Aebi U. Intermediate filaments: from cell architecture to nanomechanics. Nat. Rev. Mol. Cell Biol. 2007;8:562–573. doi: 10.1038/nrm2197. [DOI] [PubMed] [Google Scholar]
  • 7.Dechat T., Pfleghaar K., Sengupta K., Shimi T., Shumaker D.K., Solimando L., Goldman R.D. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev. 2008;22:832–853. doi: 10.1101/gad.1652708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Liu Q., Kim D.I., Syme J., LuValle P., Burke B., Roux K.J. Dynamics of lamin-A processing following precursor accumulation. PLoS One. 2010;5:e10874. doi: 10.1371/journal.pone.0010874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Prokocimer M., Davidovich M., Nissim-Rafinia M., Wiesel-Motiuk N., Bar D., Barkan R., Meshorer E., Gruenbaum Y. Nuclear lamins: key regulators of nuclear structure and activities. J. Cell. Mol. Med. 2009;13:1059–1085. doi: 10.1111/j.1582-4934.2008.00676.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Zaremba-Czogalla M., Dubińska-Magiera M., Rzepecki R. [Nowe funkcje lamin — starzy znajomi w nowym świetle] Postępy Biologii Komórki. 2010;37:1–18. [Google Scholar]
  • 11.Bonne G., Di Barletta M.R., Varnous S., Becane H.M., Hammouda H.E., Merlini L., Muntoni F., Greenberg C.R., Gary F., Urtizberea J.A., Duboc D., Fardeau M., Toniolo D., Schwartz K. Mutations in the gene encoding laminA/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nature Genet. 1999;21:285–288. doi: 10.1038/6799. [DOI] [PubMed] [Google Scholar]
  • 12.Di Barletta M., Ricci E., Galluzzi G., Tonali P., Mora M., Morandi L., Romorini A., Voit T., Orstavik K.H., Merlini L. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am. J. Hum. Genet. 2000;66:1407–1412. doi: 10.1086/302869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Muchir A., Bonne G., van der Kooi A.J., van Meegen M., Baas F., Bolhuis P.A., de Visser M., Schwartz K. 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. 2000;9:1453–1459. doi: 10.1093/hmg/9.9.1453. [DOI] [PubMed] [Google Scholar]
  • 14.Fatkin D., MacRae C., Sasaki T., Wolff M.R., Porcu M., Frenneaux M., Atherton J., Vidaillet H.J., Spudich S., De Girolami U., Seidman J.G., Seidman C., Muntoni F., Muehle G., Johson W., McDonough B. Missense mutations in the rod domain in the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. New Eng. J. Med. 1999;341:1715–1724. doi: 10.1056/NEJM199912023412302. [DOI] [PubMed] [Google Scholar]
  • 15.Bione S., Maestrini E., Rivella S., Mancini M., Regis S., Romeo G., Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat. Genet. 1994;8:323–327. doi: 10.1038/ng1294-323. [DOI] [PubMed] [Google Scholar]
  • 16.Renou L., Stora S., Yaou R.B., Volk M., Sinkovec M., Demay L., Richard P., Peterlin B., Bonne G. Heart-hand syndrome of Slovenian type: a new kind of laminopathy. J. Med. Genet. 2008;45:666–671. doi: 10.1136/jmg.2008.060020. [DOI] [PubMed] [Google Scholar]
  • 17.Cao H., Hegele R.A. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum. Mol. Genet. 2000;9:109–112. doi: 10.1093/hmg/9.1.109. [DOI] [PubMed] [Google Scholar]
  • 18.Drac H., Madej-Pilarczyk A., Gospodarczyk-Szot K., Gaweł M., Kwieciński H., Hausmanowa-Petrusewicz I. Familial partial lipodystrophy associated with the heterozygous LMNA mutation 1445G>A (Arg482Gln) in a Polish family. Neurol. Neurochir. Pol. 2010;44:291–296. doi: 10.1016/s0028-3843(14)60044-x. [DOI] [PubMed] [Google Scholar]
  • 19.Hegele R.A., Cao H., Liu D.M., Costain G.A., Charlton-Menys V., Rodger N.W., Durrington P.N. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am. J. Hum. Genet. 2006;79:383–389. doi: 10.1086/505885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Young J., Morbois-Trabut L., Couzinet B., Lascols O., Dion E., Bereziat V., Feve B., Richard I., Capeau J., Chanson P., Vigouroux C. Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes. 2005;54:1873–1878. doi: 10.2337/diabetes.54.6.1873. [DOI] [PubMed] [Google Scholar]
  • 21.De Sandre-Giovannoli A., Bernard R., Cau P., Navarro C., Amiel J., Boccaccio I., Lyonnet S., Stewart C.L., Munnich A., Le Merrer M., Levy N. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300:2055. doi: 10.1126/science.1084125. [DOI] [PubMed] [Google Scholar]
  • 22.Chen L., Lee L., Kudlow B., Dos Santos H., Sletvold O., Shafeghati Y., Botha E., Garg A., Hanson N., Martin G.M., Mian I.S., Kennedy B.K., Oshima J. LMNA mutations in atypical Werner’s syndrome. Lancet. 2003;362:440–445. doi: 10.1016/S0140-6736(03)14069-X. [DOI] [PubMed] [Google Scholar]
  • 23.Navarro C.L., Cadinanos J., De Sandre-Giovannoli A., Bernard R., Courrier S., Boccaccio I., Boyer A., Kleijer W.J., Wagner A., Giuliano F., Beemer F.A., Freije J.M., Cau P., Hennekam R.C., Lopez-Otin C., Badens C., Levy N. Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors. Hum. Mol. Genet. 2005;14:1503–1513. doi: 10.1093/hmg/ddi159. [DOI] [PubMed] [Google Scholar]
  • 24.Agarwal A.K., Fryns J.P., Auchus R.J., Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum. Mol. Genet. 2003;12:1995–2001. doi: 10.1093/hmg/ddg213. [DOI] [PubMed] [Google Scholar]
  • 25.Novelli G., Muchir A., Sangiuolo F., Helbling-Leclerc A., D’Apice M.R., Massart C., Capon F., Sbraccia P., Federici M., Lauro R., Tudisco C., Pallotta R., Scarano G., Dallapiccola B., Merlini L., Bonne G. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am. J. Hum. Genet. 2002;71:426–431. doi: 10.1086/341908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Hoffmann K., Dreger C.K., Olins A.L., Olins D.E., Shultz L.D., Lucke B., Karl H., Kaps R., Muller D., Vaya A., Aznar J., Ware R.E., Cruz N.S., Lindner T.H., Herrmann H., Reis A., Sperling K. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huet anomaly) Nat. Genet. 2002;31:410–414. doi: 10.1038/ng925. [DOI] [PubMed] [Google Scholar]
  • 27.Garg A., Subramanyam L., Agarwal A.K., Simha V., Levine B., D’Apice M.R., Novelli G., Crow Y. Atypical progeroid syndrome due to heterozygous missense LMNA mutations. J. Clin. Endocrinol. Metab. 2009;94:4971–4983. doi: 10.1210/jc.2009-0472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.De Sandre-Giovannoli A., Chaouch M., Kozlov S., Vallat J.M., Tazir M., Kassouri N., Szepetowski P., Hammadouche T., Vandenberghe A., Stewart C.L., Grid D., Levy N. 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. 2002;70:726–736. doi: 10.1086/339274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Padiath Q.S., Saigoh K., Schiffmann R., Asahara H., Yamada T., Koeppen A., Hogan K., Ptacek L.J., Fu Y.H. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat. Genet. 2006;38:1114–1123. doi: 10.1038/ng1872. [DOI] [PubMed] [Google Scholar]
  • 30.Vantyghem, M.C., Pigny, P., Maurage, C.A., Rouaix-Emery, N., Stojkovic, T., Cuisset, J.M., Millaire, A., Lascols, O., Vermersch, P., Wemeau, J.L., Capeau, J. and Vigouroux, C. Patients with familial partial lipodystrophy of the Dunnigan type due to a LMNA R482W mutation show muscular and cardiac abnormalities. J. Clin. Endocrinol. Metab. (2004) 5337–5346. [DOI] [PubMed]
  • 31.Vantyghem M.C., Faivre-Defrance F., Marcelli-Tourvieille S., Fermon C., Evrard A., Bourdelle-Hego M.F., Vigouroux C., Defebvre L., Delemer B., Wemeau J.L. Familial partial lipodystrophy due to the LMNA R482W mutation with multinodular goitre, extrapyramidal syndrome and primary hyperaldosteronism. Clin. Endocrinol (Oxf). 2007;67:247–249. doi: 10.1111/j.1365-2265.2007.02870.x. [DOI] [PubMed] [Google Scholar]
  • 32.Benedetti S., Bertini E., Iannaccone S., Angelini C., Trisciani M., Toniolo D., Sferrazza B., Carrera P., Comi G., Ferrari M., Quattrini A., Previtali S.C. Dominant LMNA mutations can cause combined muscular dystrophy and peripheral neuropathy. J. Neurol. Neurosurg. Psychiatry. 2005;76:1019–1021. doi: 10.1136/jnnp.2004.046110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Goizet C., Yaou R., Demay L., Richard P., Bouillot S., Rouanet M., Hermosilla E., Le Masson G., Lagueny A., Bonne G., Ferrer X. A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J. Med. Genet. 2004;41:e29. doi: 10.1136/jmg.2003.013383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Hegele R.A., Oshima J. Phenomics and lamins: from disease to therapy. Exp. Cell Res. 2007;313:2134–2143. doi: 10.1016/j.yexcr.2007.03.023. [DOI] [PubMed] [Google Scholar]
  • 35.Harborth J., Elbashir S.M., Bechert K., Tuschl T., Weber K. Identification of essential genes in cultured mammalian cells using small interfering RNAs. J. Cell Sci. 2001;114:4557–4565. doi: 10.1242/jcs.114.24.4557. [DOI] [PubMed] [Google Scholar]
  • 36.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. 2004;101:10428–10433. doi: 10.1073/pnas.0401424101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Coffinier C., Chang S.Y., Nobumori C., Tu Y., Farber E.A., Toth J.I., Fong L.G., Young S.G. Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. Proc. Natl. Acad. Sci. USA. 2010;107:5076–5081. doi: 10.1073/pnas.0908790107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Waterham H.R., Koster J., Mooyer P., van Noort G., Kelley R.I., Wilcox W.R., Wanders R.J.A., Hennekam R.C.M., Oosterwijk J.C. Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3betahydroxysterol delta14-reductase deficiency due to mutations in the lamin B receptor gene. Am. J. Hum. Genet. 2003;72:1013–1017. doi: 10.1086/373938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Yuste-Chaves, M., Cañueto, J., Santos-Briz, A., Ciria, S., González-Sarmiento, R. and Unamuno, P. Buschke-Ollendorff Syndrome with Striking Phenotypic Variation Resulting from a Novel c.2203C>T Nonsense Mutation in LEMD3. Pediatr. Dermatol. (2010) DOI: 10.1111/j.1525-1470.2010 [DOI] [PubMed]
  • 40.Taylor M.R., Slavov D., Gajewski A., Vlcek S., Ku L., Fain P.R., Carniel E., Di Lenarda A., Sinagra G., Boucek M.M., Cavanaugh J., Graw S.L., Ruegg P., Feiger J., Zhu X., Ferguson D.A., Bristow M.R., Gotzmann J., Foisner R., Mestroni L. Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy. Hum. Mutat. 2005;26:566–574. doi: 10.1002/humu.20250. [DOI] [PubMed] [Google Scholar]
  • 41.Landires I., Pascale J.M., Motta J. The position of the mutation within the LMNA gene determines the type and extent of tissue involvement in laminopathies. Clin. Genet. 2007;71:592–593. doi: 10.1111/j.1399-0004.2007.00772.x. [DOI] [PubMed] [Google Scholar]
  • 42.Scharner J., Gnocchi V.F., Ellis J.A., Zammit P.S. Genotypephenotype correlations in laminopathies: how does fate translate? BMC Dev. Biol. 2010;38:257–262. doi: 10.1042/BST0380257. [DOI] [PubMed] [Google Scholar]
  • 43.Simon D.N., Zastrow M.S., Wilson K.L. Direct actin binding to A- and B-type lamin tails and actin filament bundling by the lamin A tail. Nucleus. 2010;1:264–272. doi: 10.4161/nucl.1.3.11799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Magracheva E., Kozlov S., Stewart C.L., Wlodawer A., Zdanov A. Structure of the lamin A/C R482W mutant responsible for dominant familial partial lipodystrophy (FPLD) Acta Crystallogr. Sect. F: Struct. Biol. Cryst. Commun. 2009;65:665–670. doi: 10.1107/S1744309109020302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Sewry C. Muscular dystrophies: an update on pathology and diagnosis. Acta Neuropathol. 2010;120:343–358. doi: 10.1007/s00401-010-0727-5. [DOI] [PubMed] [Google Scholar]
  • 46.Rzepecki R. The nuclear lamins and nuclear envelope. Cel. Mol. Biol. Lett. 2002;7:1019–1035. [PubMed] [Google Scholar]
  • 47.Chmielewska, M., Dubińska-Magiera, M., Sopel, M., Rzepecka, D., Hutchison, C.J., Goldberg, M.W. and Rzepecki, R. Embryonic and adult isoforms of XLAP2 form microdomains associated with chromatin and the nuclear envelope. Cell Tissue Res. (2011), in press. [DOI] [PMC free article] [PubMed]
  • 48.Margalit A., Brachner A., Gotzmann J., Foisner R., Gruenbaum Y. Barrier-to-autointegration factor—a BAFfling little protein. Trends Cell Biol. 2007;17:202–208. doi: 10.1016/j.tcb.2007.02.004. [DOI] [PubMed] [Google Scholar]
  • 49.Emery A.E., Dreifuss F.E. Unusual type of benign X-linked muscular dystrophy. J. Neurol. Neurosurg. Psychiatry. 1966;29:338–342. doi: 10.1136/jnnp.29.4.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Vaughan O.A., Alvarez-Reyes M., Bridger J.M., Broers J.L.V., Ramaekers F.C.S., Wehnert M., Morris G.E., Whitfield W.G.F., Hutchison C.J. Both emerin and lamin C depend on lamin A for localization at the nuclear envelope. J. Cell Sci. 2001;114:2577–2590. doi: 10.1242/jcs.114.14.2577. [DOI] [PubMed] [Google Scholar]
  • 51.Wheeler M.A., Ellis J.A. Molecular signatures of Emery-Dreifuss muscular dystrophy. Biochem. Soc. Trans. 2008;36:1354–1358. doi: 10.1042/BST0361354. [DOI] [PubMed] [Google Scholar]
  • 52.Gueneau L., Bertrand A.T., Jais J.P., Salih M.A., Stojkovic T., Wehnert M., Hoeltzenbein M., Spuler S., Saitoh S., Verschueren A., Tranchant C., Beuvin M., Lacene E., Romero N.B., Heath S., Zelenika D., Voit T., Eymard B., Ben Yaou R., Bonne G. Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am. J. Hum. Genet. 2009;85:338–353. doi: 10.1016/j.ajhg.2009.07.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Zhang Q., Bethmann C., Worth N.F., Davies J.D., Wasner C., Feuer A., Ragnauth C.D., Yi Q., Mellad J.A., Warren D.T., Wheeler M.A., Ellis J.A., Skepper J.N., Vorgerd M., Schlotter-Weigel B., Weissberg P.L., Roberts R.G., Wehnert M., Shanahan C.M. Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum. Mol. Genet. 2007;16:2816–2833. doi: 10.1093/hmg/ddm238. [DOI] [PubMed] [Google Scholar]
  • 54.Taylor M.R.G., Fain P.R., Sinagra G., Robinson M.L., Robertson A.D., Carniel E., Di Lenarda A., Bohlmeyer T.J., Ferguson D.A., Brodsky G.L., Boucek M.M., Lascor J., Moss A.C., Li W.-L.P., Stetler G.L., Muntoni F., Bristow M.R., Mestroni L., Group F.D.C.R.R. Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. J. Am. Coll. Cardiol. 2003;41:771–780. doi: 10.1016/S0735-1097(02)02954-6. [DOI] [PubMed] [Google Scholar]
  • 55.Arbustini E., Pilotto A., Repetto A., Grasso M., Negri A., Diegoli M., Campana C., Scelsi L., Baldini E., Gavazzi A., Tavazzi L. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease. J. Am. Coll. Cardiol. 2002;39:981–990. doi: 10.1016/S0735-1097(02)01724-2. [DOI] [PubMed] [Google Scholar]
  • 56.Muchir A., Worman H.J. Emery-Dreifuss muscular dystrophy. Curr. Neurol. Neurosci. Rep. 2007;7:78–83. doi: 10.1007/s11910-007-0025-3. [DOI] [PubMed] [Google Scholar]
  • 57.Quijano-Roy S., Mbieleu B., Bönnemann C.G., Jeannet P.Y., Colomer J., Clarke N.F., Cuisset J.M., Roper H., De Meirleir L., D’Amico A., Ben Yaou R., Nascimento A., Barois A., Demay L., Bertini E., Ferreiro A., Sewry C.A., Romero N.B., Ryan M., Muntoni F., Guicheney P., Richard P., Bonne G., Estournet B. De novo LMNA mutations cause a new form of congenital muscular dystrophy. Ann. Neurol. 2008;64:177–186. doi: 10.1002/ana.21417. [DOI] [PubMed] [Google Scholar]
  • 58.Dahl K.N., Booth-Gauthier E.A., Ladoux B. In the middle of it all: mutual mechanical regulation between the nucleus and the cytoskeleton. J. Biomech. 2010;43:2–8. doi: 10.1016/j.jbiomech.2009.09.002. [DOI] [PubMed] [Google Scholar]
  • 59.Attali R., Warwar N., Israel A., Gurt I., McNally E., Puckelwartz M., Glick B., Nevo Y., Ben-Neriah Z., Melki J. Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis. Hum. Mol. Genet. 2009;18:3462–3469. doi: 10.1093/hmg/ddp290. [DOI] [PubMed] [Google Scholar]
  • 60.Gros-Louis F., Dupré N., Dion P., Fox M.A., Laurent S., Verreault S., Sanes J.R., Bouchard J.P., Rouleau G.A. Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nat. Genet. 2007;39:80–85. doi: 10.1038/ng1927. [DOI] [PubMed] [Google Scholar]
  • 61.Holaska J.M., Wilson K.L. An emerin “proteome”: purification of distinct emerincontaining complexes from HeLa cells suggests molecular basis for diverse rolesincluding gene regulation, mRNA splicing, signaling, mechanosensing, and nu clear architecture. Biochemistry. 2007;46:8897–8908. doi: 10.1021/bi602636m. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Andrés V., González J.M. Role of A-type lamins in signaling, transcription, and chromatin organization. J. Cell Biol. 2009;187:945–957. doi: 10.1083/jcb.200904124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Marmiroli S., Bertacchini J., Beretti F., Cenni V., Guida M., De Pol A., Maraldi N.M., Lattanzi G. A-type lamins and signaling: the PI 3-kinase/Akt pathway moves forward. J. Cell. Physiol. 2009;220:553–561. doi: 10.1002/jcp.21807. [DOI] [PubMed] [Google Scholar]
  • 64.Kim E.K., Choi E.J. Pathological roles of MAPK signaling pathways in human diseases. Biochim. Biophys. Acta. 2010;1802:396–405. doi: 10.1016/j.bbadis.2009.12.009. [DOI] [PubMed] [Google Scholar]
  • 65.González J.M., Navarro-Puche A., Casar B., Crespo P., Andrés V. Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. J. Cell Biol. 2008;183:653–666. doi: 10.1083/jcb.200805049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Muchir A., Pavlidis P., Bonne G., Hayashi Y.K., Worman H.J. Activation of MAPK in hearts of EMD null mice: similarities between mouse models of X-linked and autosomal dominant Emery Dreifuss muscular dystrophy. Hum. Mol. Genet. 2007;16:1884–1895. doi: 10.1093/hmg/ddm137. [DOI] [PubMed] [Google Scholar]
  • 67.Muchir A., Pavlidis P., Decostre V., Herron A.J., Arimura T., Bonne G., Worman H.J. Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J. Clin. Invest. 2007;117:1282–1293. doi: 10.1172/JCI29042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Muchir A., Wu W., Worman H.J. Reduced expression of A-type lamins and emerin activates extracellular signal-regulated kinase in cultured cells. Biochim. Biophys. Acta. 2009;1792:75–81. doi: 10.1016/j.bbadis.2008.10.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Emerson L.J., Holt M.R., Wheeler M.A., Wehnert M., Parsons M., Ellis J.A. Defects in cell spreading and ERK1/2 activation in fibroblasts with lamin A/C mutations. Biochim. Biophys. Acta. 2009;1792:810–821. doi: 10.1016/j.bbadis.2009.05.007. [DOI] [PubMed] [Google Scholar]
  • 70.Muchir A., Shan J., Bonne G., Lehnart S.E., Worman H.J. Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins. Hum. Mol. Genet. 2009;18:241–247. doi: 10.1093/hmg/ddn343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Wu W., Shan J., Bonne G., Worman H.J., Muchir A. Pharmacological inhibition of c-Jun N-terminal kinase signaling prevents cardiomyopathy caused by mutation in LMNA gene. Biochim. Biophys. Acta. 2010;1802:632–638. doi: 10.1016/j.bbadis.2010.04.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.MacDonald B.T., Tamai K., He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell. 2009;17:9–26. doi: 10.1016/j.devcel.2009.06.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Markiewicz E., Tilgner k., Barker N., van de Wetering M., Clevers H., Dorobek M., Hausmanowa-Petrusewicz I., Ramaekers F.C., Broers J.L., Blankesteijn W.M., Salpingidou G., Wilson R.G., Ellis J.A., Hutchison C.J. The inner nuclear membrane protein emerin regulates betacatenin activity by restricting its accumulation in the nucleus. EMBO J. 2006;25:3275–3285. doi: 10.1038/sj.emboj.7601230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Hoppler S., Kavanagh C.L. Wnt signalling: variety at the core. J. Cell Sci. 2007;120:385–393. doi: 10.1242/jcs.03363. [DOI] [PubMed] [Google Scholar]
  • 75.Goichberg P., Shtutman M., Ben-Zeev A., Geiger B. Recruitment of β-catenin to cadherin-mediated intercellular adhesions is involved in myogenic induction. J. Cell Sci. 2001;114:1309–1319. doi: 10.1242/jcs.114.7.1309. [DOI] [PubMed] [Google Scholar]
  • 76.Perez-Ruiz A., Ono Y., Gnocchi V.F., Zammit P.S. β-catenin promotes self-renewal of skeletal-muscle satellite cells. J. Cell Sci. 2008;121:1373–1382. doi: 10.1242/jcs.024885. [DOI] [PubMed] [Google Scholar]
  • 77.Hutchison C.J., Worman H.J. A-type lamins: Guardians of the soma? Nat. Cell Biol. 2004;6:1062–1067. doi: 10.1038/ncb1104-1062. [DOI] [PubMed] [Google Scholar]
  • 78.Johnson B.R. A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc. Natl. Acad. Sci. USA. 2004;101:9677–9682. doi: 10.1073/pnas.0403250101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Markiewicz E., Dechat T., Foisner R., Quinlan R.A., Hutchison C.J. Lamin A/C binding protein LAP2 alpha is required for nuclear anchorage of retinoblastoma protein. Mol. Biol. Cell. 2002;13:4401–4413. doi: 10.1091/mbc.E02-07-0450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Frock R.L., Kudlow B.A., Evans A.M., Jameson S.A., Hauschka S.D., Kennedy B.K. Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev. 2006;20:486–500. doi: 10.1101/gad.1364906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Naetar N., Foisner R. Lamin complexes in the nuclear interior control progenitor cell proliferation and tissue homeostasis. Cell Cycle. 2009;8:1488–1493. doi: 10.4161/cc.8.10.8499. [DOI] [PubMed] [Google Scholar]
  • 82.Massagué J. How cells read TGF-beta signals. Nat. Rev. Mol. Cell Biol. 2000;1:169–178. doi: 10.1038/35043051. [DOI] [PubMed] [Google Scholar]
  • 83.Van Berlo, J.H., Voncken, J.W., Kubben, N., Broers, J.L., Duisters, R., van Leeuwen, R.E., Crijns, H.J., Ramaekers, F.C., Hutchison, C.J. and Pinto, Y.M. A-type lamins are essential for TGF-ta1 induced PP2A to dephosphorylate transcription factors. Hum. Mol. Genet.14 (2005) 2839–2849. [DOI] [PubMed]
  • 84.Puri P.L., Iezzi S., Stiegler P., Chen T.T., Schiltz R.L., Muscat G.E., Giordano A., Kedes L., Wang J.Y., Sartorelli V. Class I histone deacetylases sequentially interact with MyoD and pRb during skeletal myogenesis. Mol. Cell. 2001;8:885–897. doi: 10.1016/S1097-2765(01)00373-2. [DOI] [PubMed] [Google Scholar]
  • 85.Park Y.E., Hayashi Y.K., Goto K., Komaki H., Hayashi Y., Inuzuka T., Noguchi S., Nonaka I., Nishino I. Nuclear changes in skeletal muscle extend to satellite cells in autosomal dominant Emery-Dreifuss muscular dystrophy/limb-girdle muscular dystrophy 1B. Neuromuscul. Disord. 2008;19:29–36. doi: 10.1016/j.nmd.2008.09.018. [DOI] [PubMed] [Google Scholar]
  • 86.Meshorer E., Gruenbaum Y. Gone with the Wnt/Notch: stem cells in laminopathies, progeria, and aging. J. Cell Biol. 2008;181:9–13. doi: 10.1083/jcb.200802155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Jones D.L., Wagers A.J. No place like home: anatomy and function of the stem cell niche. Nat. Rev. Mol. Cell. Biol. 2008;9:11–21. doi: 10.1038/nrm2319. [DOI] [PubMed] [Google Scholar]
  • 88.Favreau C., Higuet D., Courvalin J.C., Buendia B. Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts. Mol. Cell. Biol. 2004;24:1481–1492. doi: 10.1128/MCB.24.4.1481-1492.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Takai H., Yamada T., Tada S., Matsumaru I. Successful surgical repair for Emery-Dreifuss muscular dystrophy valvular disease with longterm follow-up. Interac. Cardiovasc. Thorac. Surg. 2010;10:811–812. doi: 10.1510/icvts.2009.221671. [DOI] [PubMed] [Google Scholar]
  • 90.Dechat T., Shimi T., Adam S.A., Rusinol A.E., Andres D.A., Spielmann H.P., Sinensky M.S., Goldman R.D. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc. Natl. Acad. Sci. USA. 2007;104:4955–4960. doi: 10.1073/pnas.0700854104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Rodriguez S., Coppedè F., Sagelius H., Eriksson M. Increased expression of the Hutchinson-Gilford progeria syndrome truncated lamin A transcript during cell aging. Eur. J. Hum. Genet. 2009;17:928–937. doi: 10.1038/ejhg.2008.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Goldman R.D., Shumaker D.K., Erdos M.R., Eriksson M., Goldman A.E., Gordon L.B., Gruenbaum Y., Khuon S., Mendez M., Varga R., Collins F.S. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc. Natl. Acad. Sci. USA. 2004;101:8963–8968. doi: 10.1073/pnas.0402943101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.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. 2005;102:14416–14421. doi: 10.1073/pnas.0503712102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94.Toth J.I., Yang S.H., Qiao X., Beigneux A.P., Gelb M.H., Moulson C.L., Miner J.H., Young S.G., Fong L.G. Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc. Natl. Acad. Sci. USA. 2005;102:12873–12878. doi: 10.1073/pnas.0505767102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 95.Capell B.C., Olive M., Erdos M.R., Cao K., Faddah D.A., Tavarez U.L., Conneely K.N., Qu X., San H., Ganesh S.K., Chen X., Avallone H., Kolodgie F.D., Virmani R., Nabel E.G., Collins F.S. A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proc. Natl. Acad. Sci. USA. 2008;105:15902–15907. doi: 10.1073/pnas.0807840105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96.Yang S.H., Qiao X., Fong L.G., Youn S.G. Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation. Biochim. Biophys. Acta. 2008;1781:36–39. doi: 10.1016/j.bbalip.2007.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.Yang S.H., Andres D.A., Spielmann H.P., Young S.G., Fong L.G. Progerin elicits disease phenotypes of progeria in mice whether or not it is farnesylated. J. Clin. Invest. 2008;118:3291–3300. doi: 10.1172/JCI35876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Varela I., Pereira S., Ugalde A.P., Navarro C.L., Suárez M.F., Cau P., Cadiñanos J., Osorio F.G., Cobo J., de Carlos F., Lèvy N., Freije J.M.P., López-Otín C. Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat. Med. 2008;14:767–772. doi: 10.1038/nm1786. [DOI] [PubMed] [Google Scholar]
  • 99.Kieran M.W., Gordon L., Kleinman M. New approaches to progeria. Pediatrics. 2007;120:834–841. doi: 10.1542/peds.2007-1356. [DOI] [PubMed] [Google Scholar]
  • 100.Davies B.S., Barnes R.H., Tu Y., Ren S., Andres D.A., Spielmann H.P., Lammerding J., Wang Y., Young S.G., Fong L.G. An accumulation of non-farnesylated pre-lamin A causes cardiomyopathy but not progeria. Hum. Mol. Genet. 2010;19:2682–2694. doi: 10.1093/hmg/ddq158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 101.Caron M., Auclair M., Donadille B., Béréziat V., Guerci B., Laville M., Narbonne H., Bodemer C., Lascols O., Capeau J., Vigouroux C. Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with pre-lamin A accumulation, oxidative stress and premature cellular senescence. Cell Death Differ. 2007;14:1759–1767. doi: 10.1038/sj.cdd.4402197. [DOI] [PubMed] [Google Scholar]
  • 102.Coffinier C., Hudon S.E., Farber E.A., Chang S.Y., Hrycyna C.A., Young S.G., Fong L.G. HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of pre-lamin A in cells. Proc. Natl. Acad. Sci. USA. 2007;104:13432–13437. doi: 10.1073/pnas.0704212104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 103.Huang, S., Chen, L., Libina, N., Janes, J., Martin, G.M., Campisi, J. and Oshima, J. Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference. Hum. Genet. (2005) 1–7. [DOI] [PubMed]
  • 104.Fong L.G., Ng J.K., Lammerding J., Vickers T.A., Meta M., Cote N., Gavino B., Qiao X., Chang S.Y., Young S.R., Yang S.H., Stewart C.L., Lee R.T., Bennett C.F., Bergo M.O., Young S.G. Pre-lamin A and lamin A appear to be dispensable in the nuclear lamina. J. Clin. Invest. 2006;116:743–752. doi: 10.1172/JCI27125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 105.Fong L.G., Vickers T.A., Farber E.A., Choi C., Yun U.J., Hu Y., Yang S.H., Coffinier C., Lee R., Yin L., Davies B.S., Andres D.A., Spielmann H.P., Bennett C.F., Young S. Activating the synthesis of progerin, the mutant pre-lamin A in Hutchinson-Gilford progeria syndrome, with antisense oligonucleotides. Hum. Mol. Genet. 2009;18:2462–2471. doi: 10.1093/hmg/ddp184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 106.Marji, J., O’Donoghue, S.I., McClintock, D., Satagopam, V.P., Schneider, R., Ratner, D., Worman, H., Gordon, L.B. and Djabali, K. Defective lamin A-Rb signaling in Hutchinson-Gilford Progeria Syndrome and reversal by farnesyltransferase inhibition. PLoS One5 (2010) e11132. [DOI] [PMC free article] [PubMed]
  • 107.Scaffidi P., Misteli T. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat. Cell Biol. 2008;10:452–459. doi: 10.1038/ncb1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 108.Scaffidi P., Misteli T. Lamin A-dependent nuclear defects in human aging. Science. 2006;312:1059–1063. doi: 10.1126/science.1127168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 109.Espada J., Varela I., Flores I., Ugalde A.P., Cadinanos J., Pendas A.M., Stewar C.L., Tryggvason K., Blasco M.A., Freije J.M., Lopez-Otin C. Nuclear envelope defects cause stem cell dysfunction in premature-aging mice. J. Cell Biol. 2008;181:27–35. doi: 10.1083/jcb.200801096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 110.Hegele R.A., Joy T.R., Al-Attar S.A., Rutt B.K. Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism. J. Lipid Res. 2007;48:1433–1444. doi: 10.1194/jlr.R700004-JLR200. [DOI] [PubMed] [Google Scholar]
  • 111.Tilgner, K., Wojciechowicz, K., Jahoda, C., Hutchison, C. and Markiewicz, E. Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of ta-catenin. J. Cell Sci.122 (2009) 401–413. [DOI] [PMC free article] [PubMed]
  • 112.Christodoulides C., Lagathu C., Sethi J.K., Vidal-Puig A. Adipogenesis and WNT signalling. Trends Endocrinol. Metab. 2009;20:16–24. doi: 10.1016/j.tem.2008.09.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 113.Guillet-Deniau I., Pichard A.-L., Kone A., Esnous C., Nieruchalski M., Girard J., Prip-Buus C. Glucose induces de novo lipogenesis in rat muscle satellite cells through a sterol-regulatory-element-binding-protein-1c-dependent pathway. J. Cell Sci. 2004;117:1937–1944. doi: 10.1242/jcs.01069. [DOI] [PubMed] [Google Scholar]
  • 114.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. 2002;11:769–777. doi: 10.1093/hmg/11.7.769. [DOI] [PubMed] [Google Scholar]
  • 115.Javor E.D., Cochran E.K., Musso C., Young J.R., Depaoli A.M., Gorden P. Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes. 2005;54:1994–2002. doi: 10.2337/diabetes.54.7.1994. [DOI] [PubMed] [Google Scholar]
  • 116.Park J.Y., Javor E.D., Cochran E.K., DePaoli A.M., Gorden P. Longterm efficacy of leptin replacement in patients with Dunnigan-type familial partial lipodystrophy. Metabolism. 2007;56:508–516. doi: 10.1016/j.metabol.2006.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 117.Maraldi N.M., Capanni C., Lattanzi G., Camozzi D., Facchini A., Manzoli F.A. SREBP1 interaction with pre-lamin A forms: a pathogenic mechanism for lipodystrophic laminopathies. Adv. Enzyme Regul. 2008;48:209–223. doi: 10.1016/j.advenzreg.2007.11.003. [DOI] [PubMed] [Google Scholar]
  • 118.Broers J.L., Ramaekers F.C., Bonne G., Yaou R.B., Hutchison C.J. Nuclear lamins: laminopathies and their role in premature ageing. Physiol. Rev. 2006;86:967–1008. doi: 10.1152/physrev.00047.2005. [DOI] [PubMed] [Google Scholar]
  • 119.Méjat A.V., Decostre J., Li L., Renou A., Kesari D., Hantaï C.L., Stewart X., Xiao E., Hoffman G., Bonne G., Misteli T. Lamin A/C — mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy. J. Cell Biol. 2009;184:31–44. doi: 10.1083/jcb.200811035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 120.Bridger J.M., Foeger N., Kill I.R., Herrmann H. The nuclear lamina. Both a structural framework and a platform for genome organization. FEBS J. 2007;274:1354–1361. doi: 10.1111/j.1742-4658.2007.05694.x. [DOI] [PubMed] [Google Scholar]
  • 121.Wilson, K.L. and Foisner, R. Lamin-binding Proteins. Cold Spring Harb Perspect. Biol.2 (2010) a000554. [DOI] [PMC free article] [PubMed]
  • 122.Rzepecki R., Fisher P.A. In vivo phosphorylation of Drosophila melanogaster nuclear lamins during both interphase and mitosis. Cell. Mol. Biol. Lett. 2002;7:859–876. [PubMed] [Google Scholar]
  • 123.Zhang Y.Q., Sarge K.D. Sumoylation regulates lamin A function and is lost in lamin A mutants associated with familial cardiomyopathies. J. Cell Biol. 2008;182:35–39. doi: 10.1083/jcb.200712124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.Cenni V., Bertacchini J., Beretti F., Lattanzi G., Bavelloni A., Riccio M., Ruzzene M., Marin O., Arrigoni G., Parnaik V., Wehnert M., Maraldi N.M., de Pol A., Cocco L., Marmiroli S. Lamin A Ser404 is a nuclear target of Akt phosphorylation in C2C12 cells. J. Proteome Res. 2008;7:4727–4735. doi: 10.1021/pr800262g. [DOI] [PubMed] [Google Scholar]
  • 125.Tifft K.E., Bradbury K.A., Wilson K.L. Tyrosine phosphorylation of nuclear-membrane protein emerin by Src, Abl and other kinases. J. Cell Sci. 2009;122:3780–3790. doi: 10.1242/jcs.048397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 126.Sullivan T., Escalante-Alcalde D., Bhatt H., Anver M., Bhat N., Nagashima K., Stewart C.L., Burke B. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 1999;147:913–920. doi: 10.1083/jcb.147.5.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 127.Leung G.K., Schmidt W.K., Bergo M.O., Gavino B., Wong D.H., Tam A., Ashby M.N., Michaelis S., Young S.G. Biochemical studies of Zmpste24-deficient mice. J. Biol. Chem. 2001;276:29051–29058. doi: 10.1074/jbc.M102908200. [DOI] [PubMed] [Google Scholar]
  • 128.Ozawa R., Hayashi Y.K., Ogawa M., Kurokawa R., Matsumoto H., Noguchi S., Nonaka I., Nishino I. Emerin-lacking mice show minimal motor and cardiac dysfunctions with nuclear-associated vacuoles. Am. J. Pathol. 2006;186:907–917. doi: 10.2353/ajpath.2006.050564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 129.Arimura T., Helbling-Leclerc A., Massart C., Varnous S., Niel F., Lacene E., Fromes Y., Toussaint M., Mura A.M., Keller D.I., Amthor H., Isnard R., Malissen M., Schwartz K., Bonne G. Mouse model carrying H222P-LMNA mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum. Mol. Genet. 2005;14:155–169. doi: 10.1093/hmg/ddi017. [DOI] [PubMed] [Google Scholar]
  • 130.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. 2006;14:2167–2180. doi: 10.1093/hmg/ddi221. [DOI] [PubMed] [Google Scholar]
  • 131.Wang Y., Herron A.J., Worman H.J. Pathology and nuclear abnormalities in hearts of transgenic mice expressing M371K lamin A encoded by an LMNA mutation causing Emery-Dreifuss muscular dystrophy. Hum. Mol. Genet. 2006;15:2479–2489. doi: 10.1093/hmg/ddl170. [DOI] [PubMed] [Google Scholar]
  • 132.Nikolova V., Leimena C., McMahon A.C., Tan J.C., Chandar S., Jogia D., Kesteven S.H., Michalicek J., Otway R., Verheyen F., Rainer S., Stewart C.L., Martin D., Feneley M.P., Fatkin D. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/Cdeficient mice. J. Clin. Invest. 2004;113:357–369. doi: 10.1172/JCI19448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 133.Alsheimer M., Liebe B., Sewell L., Stewart C.L., Scherthan H., Benavente R. Disruption of spermatogenesis in mice lacking A-type lamins. J. Cell Sci. 2004;117:1173–1178. doi: 10.1242/jcs.00975. [DOI] [PubMed] [Google Scholar]
  • 134.Hale J.S., Frock R.L., Mamman S.A., Fink P.J., Kennedy B.K. Cellextrinsic defective lymphocyte development in Lmna−/− mice. PLoS One. 2010;5:e10127. doi: 10.1371/journal.pone.0010127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 135.Bergo M.O. Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a pre-lamin A processing defect. Proc. Natl. Acad. Sci. USA. 2002;99:13049–13054. doi: 10.1073/pnas.192460799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 136.Anjos-Afonso F., Siapati E.K., Bonnet D. In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions. J. Cell Sci. 2004;117:5655–5664. doi: 10.1242/jcs.01488. [DOI] [PubMed] [Google Scholar]
  • 137.Cousins J.C., Woodward K.J., Gross J.G., Partridge T.A., Morgan J.E. Regeneration of skeletal muscle from transplanted immortalised myoblasts is oligoclonal. J. Cell Sci. 2004;117:3259–3269. doi: 10.1242/jcs.01161. [DOI] [PubMed] [Google Scholar]
  • 138.D`Ippolito G., Diabira S., Howard G.A., Menei P., Roos B.A., Schiller P.C. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J. Cell Sci. 2004;117:2971–2981. doi: 10.1242/jcs.01103. [DOI] [PubMed] [Google Scholar]
  • 139.Mazhari R., Hare J.M. Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat. Clin. Pract. Cardiovasc. Med. 2007;4:S21–26. doi: 10.1038/ncpcardio0770. [DOI] [PubMed] [Google Scholar]
  • 140.Dwyer R.M., Khan S., Barry F.P., O’Brien T., Kerin M.J. Advances in mesenchymal stem cell-mediated gene therapy for cancer. Stem Cell Res. Ther. 2010;1:25. doi: 10.1186/scrt25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 141.Pistoia V., Raffaghello L. Potential of mesenchymal stem cells for the therapy of autoimmune diseases. Expert Rev. Clin. Immunol. 2010;6:211–218. doi: 10.1586/eci.09.86. [DOI] [PubMed] [Google Scholar]
  • 142.Griffin M., Greiser U., Barry F., O’Brien T., Ritter T. Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease. Discov. Med. 2010;9:219–223. [PubMed] [Google Scholar]
  • 143.Epting C.L., Lopez J.E., Shen X., Liu L., Bristow J., Bernstein H.S. Stem cell antigen-1 is necessary for cell-cycle withdrawal and myoblast differentiation in C2C12 cells. J. Cell Sci. 2004;117:6185–6195. doi: 10.1242/jcs.01548. [DOI] [PubMed] [Google Scholar]
  • 144.Rivier F., Alkan O., Flint A.F., Muskiewicz K., Allen P.D., Leboulch P., Gussoni E. Role of bone marrow cell trafficking in replenishing skeletal muscle SP and MP cell populations. J. Cell Sci. 2004;117:1979–1988. doi: 10.1242/jcs.01051. [DOI] [PubMed] [Google Scholar]
  • 145.Banasik M.B., McCray P.B.J. Integrase-defective lentiviral vectors: progress and applications. Gene Ther. 2010;17:150–157. doi: 10.1038/gt.2009.135. [DOI] [PubMed] [Google Scholar]
  • 146.Cartier N., Hacein-Bey-Abina S., Bartholomae C.C., Veres G., Schmidt M., Kutschera I., Vidaud M., Abel U., Dal-Cortivo L., Caccavelli L., Mahlaoui N., Kiermer V., Mittelstaedt D., Bellesme C., Lahlou N., Lefrère F., Blanche S., Audit M., Payen E., Leboulch P., l’Homme B., Bougnères P., Von Kalle C., Fischer A., Cavazzana-Calvo M., Aubourg P. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science. 2009;326:818–823. doi: 10.1126/science.1171242. [DOI] [PubMed] [Google Scholar]

Articles from Cellular & Molecular Biology Letters are provided here courtesy of BMC

RESOURCES