Regulation of Myelination in the Central Nervous System by Nuclear Lamin B1 and Non-coding RNAs

Translational Neurodegeneration

Ying-Hui Fu²  Louis J Ptáček¹  Mary Y Heng²  Shu-Ting Lin² 

[1] Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA;Department of Neurology, University of California, 1550 Fourth street, UCSF-Mission Bay, Rock Hall 548, San Francisco, CA 94158, USA

关键词: Myelin;    MicroRNA;    Long non-coding RNA;    Lamin;   

Others  :  838450
DOI  :  10.1186/2047-9158-3-4

 received in 2013-12-11, accepted in 2014-02-01,  发布年份 2014

【 摘 要 】

Adult-onset autosomal dominant leukodystrophy (ADLD) is a progressive and fatal hereditary demyelination disorder characterized initially by autonomic dysfunction and loss of myelin in the central nervous system (CNS). Majority of ADLD is caused by a genomic duplication of the nuclear lamin B1 gene (LMNB1) encoding lamin B1 protein, resulting in increased gene dosage in brain tissue. In vitro, excessive lamin B1 at the cellular level reduces transcription of myelin genes, leading to premature arrest of oligodendrocyte differentiation. Murine models of ADLD overexpressing LMNB1 exhibited age-dependent motor deficits and myelin defects, which are associated with reduced occupancy of the Yin Yang 1 transcription factor at the promoter region of the proteolipid protein gene. Lamin B1 overexpression mediates oligodendrocyte cell-autonomous neuropathology in ADLD and suggests lamin B1 as an important regulator of myelin formation and maintenance during aging. Identification of microRNA-23 (miR-23) as a negative regulator of lamin B1 can ameliorate the consequences of excessive lamin B1 at the cellular level. miR-23a-overexpressing mice display enhanced oligodendrocyte differentiation and myelin synthesis. miR-23a targets include a protein coding transcript PTEN (phosphatase and tensin homolog on chromosome 10), and a long noncoding RNA (2700046G09Rik), indicating a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin. Here, we provide a concise review of the current literature on clinical presentations of ADLD and how lamin B1 affects myelination and other developmental processes. Moreover, we address the emerging role of non-coding RNAs (ncRNAs) in modulating gene networks, specifically investigating miR-23 as a potential target for the treatment of ADLD and other demyelinating disorders.

【 授权许可】

   
2014 Lin et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Emery B: Regulation of oligodendrocyte differentiation and myelination. Science 2010, 330:779-782.
• [2]Barres BA: The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 2008, 60:430-440.
• [3]Aguirre A, Dupree JL, Mangin JM, Gallo V: A functional role for EGFR signaling in myelination and remyelination. Nat Neurosci 2007, 10:990-1002.
• [4]Rivers LE, Young KM, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, Richardson WD: PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 2008, 11:1392-1401.
• [5]Noble M: Precursor cell transitions in oligodendrocyte development. J Cell Biol 2000, 148:839-842.
• [6]Kriegstein A, Alvarez-Buylla A: The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 2009, 32:149-184.
• [7]Zhou Q, Choi G, Anderson DJ: The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron 2001, 31:791-807.
• [8]Lu QR, Sun T, Zhu Z, Ma N, Garcia M, Stiles CD, Rowitch DH: Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 2002, 109:75-86.
• [9]Parras CM, Hunt C, Sugimori M, Nakafuku M, Rowitch D, Guillemot F: The proneural gene Mash1 specifies an early population of telencephalic oligodendrocytes. J Neurosci 2007, 27:4233-4242.
• [10]Qi Y, Cai J, Wu Y, Wu R, Lee J, Fu H, Rao M, Sussel L, Rubenstein J, Qiu M: Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 2001, 128:2723-2733.
• [11]He Y, Dupree J, Wang J, Sandoval J, Li J, Liu H, Shi Y, Nave KA, Casaccia-Bonnefil P: The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron 2007, 55:217-230.
• [12]Wegner M: Expression of transcription factors during oligodendroglial development. Microsc Res Tech 2001, 52:746-752.
• [13]Clevers H: Wnt/beta-catenin signaling in development and disease. Cell 2006, 127:469-480.
• [14]Wang S, Sdrulla A, Johnson JE, Yokota Y, Barres BA: A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development. Neuron 2001, 29:603-614.
• [15]Kondo T, Raff M: The Id4 HLH protein and the timing of oligodendrocyte differentiation. EMBO J 2000, 19:1998-2007.
• [16]Liu A, Li J, Marin-Husstege M, Kageyama R, Fan Y, Gelinas C, Casaccia-Bonnefil P: A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players. EMBO J 2006, 25:4833-4842.
• [17]Stolt CC, Schlierf A, Lommes P, Hillgartner S, Werner T, Kosian T, Sock E, Kessaris N, Richardson WD, Lefebvre V, Wegner M: SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Dev Cell 2006, 11:697-709.
• [18]Padiath QS, Saigoh K, Schiffmann R, Asahara H, Yamada T, Koeppen A, Hogan K, Ptacek LJ, Fu YH: Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet 2006, 38:1114-1123.
• [19]Meijer IA, Simoes-Lopes AA, Laurent S, Katz T, St-Onge J, Verlaan DJ, Dupre N, Thibault M, Mathurin J, Bouchard JP, Rouleau GA: A novel duplication confirms the involvement of 5q23.2 in autosomal dominant leukodystrophy. Arch Neurol 2008, 65:1496-1501.
• [20]Schuster J, Sundblom J, Thuresson AC, Hassin-Baer S, Klopstock T, Dichgans M, Cohen OS, Raininko R, Melberg A, Dahl N: Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. Neurogenetics 2011, 12:65-72.
• [21]Molloy A, Cotter O, van Spaendonk R, Sistermans E, Sweeney B: A patient with a rare leukodystrophy related to lamin B1 duplication. Ir Med J 2012, 105:186-187.
• [22]Dos Santos MM, Grond-Ginsbach C, Aksay SS, Chen B, Tchatchou S, Wolf NI, van der Knaap MS, Grau AJ: Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. J Neurol 2012, 259:579-581.
• [23]Giorgio E, Rolyan H, Kropp L, Chakka AB, Yatsenko S, Gregorio ED, Lacerenza D, Vaula G, Talarico F, Mandich P, et al.: Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression. Hum Mutat 2013, 34:1160-1171.
• [24]Brussino A, Vaula G, Cagnoli C, Mauro A, Pradotto L, Daniele D, Di Gregorio E, Barberis M, Arduino C, Squadrone S, et al.: A novel family with Lamin B1 duplication associated with adult-onset leucoencephalopathy. J Neurol Neurosurg Psychiatry 2009, 80:237-240.
• [25]Brussino A, Vaula G, Cagnoli C, Panza E, Seri M, Di Gregorio E, Scappaticci S, Camanini S, Daniele D, Bradac GB, et al.: A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations. Eur J Neurol 2010, 17:541-549.
• [26]Lin ST, Fu YH: miR-23 regulation of lamin B1 is crucial for oligodendrocyte development and myelination. Dis Model Mech 2009, 2:178-188.
• [27]Eldridge R, Anayiotos CP, Schlesinger S, Cowen D, Bever C, Patronas N, McFarland H: Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. N Engl J Med 1984, 311:948-953.
• [28]Asahara H, Yoshimura T, Sada S, Furuya H, Kobayashi T: [A Japanese family with probably autosomal dominant adult-onset leukodystrophy]. Rinsho Shinkeigaku = Clinical Neurology 1996, 36:968-972.
• [29]Marklund L, Melin M, Melberg A, Giedraitis V, Dahl N: Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. Am J Med Genet B Neuropsychiatr Genet 2006, 141B:608-614.
• [30]Melberg A, Hallberg L, Kalimo H, Raininko R: MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. AJNR Am J Neuroradiol 2006, 27:904-911.
• [31]Potic A, Pavlovic AM, Uziel G, Kozic D, Ostojic J, Rovelli A, Sternic N, Bjelan M, Sarto E, Di Bella D, Taroni F: Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. J Neurol 2013, 260:2124-2129.
• [32]Quattrocolo G, Leombruni S, Vaula G, Bergui M, Riva A, Bradac GB, Bergamini L: Autosomal dominant late-onset leukoencephalopathy: clinical report of a new Italian family. Eur Neurol 1997, 37:53-61.
• [33]Abe K, Ikeda M, Watase K, Tanabe H, Fujimura H, Yorifuji S, Ueno S, Mezaki T, Mori T: A kindred of hereditary adult-onset leukodystrophy with sparing of the optic radiations. Neuroradiology 1993, 35:281-283.
• [34]Schwankhaus JD, Patronas N, Dorwart R, Eldridge R, Schlesinger S, McFarland H: Computed tomography and magnetic resonance imaging in adult-onset leukodystrophy. Arch Neurol 1988, 45:1004-1008.
• [35]Coffeen CM, McKenna CE, Koeppen AH, Plaster NM, Maragakis N, Mihalopoulos J, Schwankhaus JD, Flanigan KM, Gregg RG, Ptacek LJ, Fu YH: Genetic localization of an autosomal dominant leukodystrophy mimicking chronic progressive multiple sclerosis to chromosome 5q31. Hum Mol Genet 2000, 9:787-793.
• [36]Guaraldi P, Donadio V, Capellari S, Contin M, Casadio MC, Montagna P, Liguori R, Cortelli P: Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy. Auton Neurosci 2011, 159:123-126.
• [37]Cortelli P, Terlizzi R, Capellari S, Benarroch E: Nuclear lamins: functions and clinical implications. Neurology 2012, 79:1726-1731.
• [38]Brown RT, Polinsky RJ, Schwankhaus J, Eldridge R, McFarland H, Schlesinger S, Dailey WA: Adrenergic dysfunction in hereditary adult-onset leukodystrophy. Neurology 1987, 37:1421-1424.
• [39]Bergui M, Bradac GB, Leombruni S, Vaula G, Quattrocolo G: MRI and CT in an autosomal-dominant, adult-onset leukodystrophy. Neuroradiology 1997, 39:423-426.
• [40]Sundblom J, Melberg A, Kalimo H, Smits A, Raininko R: MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. AJNR Am J Neuroradiol 2009, 30:328-335.
• [41]Dechat T, Gesson K, Foisner R: Lamina-independent lamins in the nuclear interior serve important functions. Cold Spring Harb Symp Quant Biol 2010, 75:533-543.
• [42]Liu J, Rolef Ben-Shahar T, Riemer D, Treinin M, Spann P, Weber K, Fire A, Gruenbaum Y: Essential roles for Caenorhabditis elegans lamin gene in nuclear organization, cell cycle progression, and spatial organization of nuclear pore complexes. Mol Biol Cell 2000, 11:3937-3947.
• [43]Wagner N, Weber D, Seitz S, Krohne G: The lamin B receptor of Drosophila melanogaster. J Cell Sci 2004, 117:2015-2028.
• [44]Worman HJ, Ostlund C, Wang Y: Diseases of the nuclear envelope. Cold Spring Harb Perspect Biol 2010, 2:a000760.
• [45]Worman HJ, Bonne G: “Laminopathies”: a wide spectrum of human diseases. Exp Cell Res 2007, 313:2121-2133.
• [46]Schreiber KH, Kennedy BK: When lamins go bad: nuclear structure and disease. Cell 2013, 152:1365-1375.
• [47]Burke B, Stewart CL: The nuclear lamins: flexibility in function. Nat Rev Mol Cell Biol 2013, 14:13-24.
• [48]Vlcek S, Foisner R: Lamins and lamin-associated proteins in aging and disease. Curr Opin Cell Biol 2007, 19:298-304.
• [49]Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E, Perry P, Ylstra B, Chubb JR, Bickmore WA: Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 2008, 4:e1000039.
• [50]Reddy KL, Zullo JM, Bertolino E, Singh H: Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 2008, 452:243-247.
• [51]Vergnes L, Peterfy M, Bergo MO, Young SG, Reue K: Lamin B1 is required for mouse development and nuclear integrity. Proc Natl Acad Sci USA 2004, 101:10428-10433.
• [52]Coffinier C, Jung HJ, Nobumori C, Chang S, Tu Y, Barnes RH 2nd, Yoshinaga Y, de Jong PJ, Vergnes L, Reue K, et al.: Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons. Molec Biol Cell 2011, 22:4683-4693.
• [53]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 USA 2004, 101:8963-8968.
• [54]Dauer WT, Worman HJ: The nuclear envelope as a signaling node in development and disease. Dev Cell 2009, 17:626-638.
• [55]Hegele RA, Cao H, Liu DM, Costain GA, Charlton-Menys V, Rodger NW, Durrington PN: Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet 2006, 79:383-389.
• [56]Shimi T, Butin-Israeli V, Adam SA, Hamanaka RB, Goldman AE, Lucas CA, Shumaker DK, Kosak ST, Chandel NS, Goldman RD: The role of nuclear lamin B1 in cell proliferation and senescence. Genes & Dev 2011, 25:2579-2593.
• [57]Dreesen O, Chojnowski A, Ong PF, Zhao TY, Common JE, Lunny D, Lane EB, Lee SJ, Vardy LA, Stewart CL, Colman A: Lamin B1 fluctuations have differential effects on cellular proliferation and senescence. J Cell Biol 2013, 200:605-617.
• [58]Freund A, Laberge RM, Demaria M, Campisi J: Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 2012, 23:2066-2075.
• [59]Barascu A, Le Chalony C, Pennarun G, Genet D, Imam N, Lopez B, Bertrand P: Oxidative stress induces an ATM-independent senescence pathway through p38 MAPK-mediated lamin B1 accumulation. EMBO J 2012, 31:1080-1094.
• [60]Yang SH, Chang SY, Yin L, Tu Y, Hu Y, Yoshinaga Y, de Jong PJ, Fong LG, Young SG: An absence of both lamin B1 and lamin B2 in keratinocytes has no effect on cell proliferation or the development of skin and hair. Hum Mol Genet 2011, 20:3537-3544.
• [61]Yang SH, Jung HJ, Coffinier C, Fong LG, Young SG: Are B-type lamins essential in all mammalian cells? Nucleus 2011, 2:562-569.
• [62]Kim Y, Sharov AA, McDole K, Cheng M, Hao H, Fan CM, Gaiano N, Ko MS, Zheng Y: Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells. Science 2011, 334:1706-1710.
• [63]Pickersgill H, Kalverda B, de Wit E, Talhout W, Fornerod M, van Steensel B: Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet 2006, 38:1005-1014.
• [64]Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W, van Steensel B: Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 2008, 453:948-951.
• [65]Towbin BD, Meister P, Gasser SM: The nuclear envelope–a scaffold for silencing? Curr Opin Genet Dev 2009, 19:180-186.
• [66]Peric-Hupkes D, Meuleman W, Pagie L, Bruggeman SW, Solovei I, Brugman W, Graf S, Flicek P, Kerkhoven RM, van Lohuizen M, et al.: Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol Cell 2010, 38:603-613.
• [67]Chen H, Chen X, Zheng Y: The nuclear lamina regulates germline stem cell niche organization via modulation of EGFR signaling. Cell Stem Cell 2013, 13:73-86.
• [68]Coffinier C, Chang SY, Nobumori C, Tu Y, Farber EA, Toth JI, Fong LG, Young SG: Abnormal development of the cerebral cortex and cerebellum in the setting of lamin B2 deficiency. Proc Natl Acad Sci USA 2010, 107:5076-5081.
• [69]Coffinier C, Fong LG, Young SG: LINCing lamin B2 to neuronal migration: growing evidence for cell-specific roles of B-type lamins. Nucleus 2010, 1:407-411.
• [70]Ji JY, Lee RT, Vergnes L, Fong LG, Stewart CL, Reue K, Young SG, Zhang Q, Shanahan CM, Lammerding J: Cell nuclei spin in the absence of lamin b1. J Biol Chem 2007, 282:20015-20026.
• [71]Tsai MY, Wang S, Heidinger JM, Shumaker DK, Adam SA, Goldman RD, Zheng Y: A mitotic lamin B matrix induced by RanGTP required for spindle assembly. Science 2006, 311:1887-1893.
• [72]Stuurman N, Heins S, Aebi U: Nuclear lamins: their structure, assembly, and interactions. J Struct Biol 1998, 122:42-66.
• [73]Jung HJ, Nobumori C, Goulbourne CN, Tu Y, Lee JM, Tatar A, Wu D, Yoshinaga Y, de Jong PJ, Coffinier C, et al.: Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration. Proc Natl Acad Sci USA 2013, 110:E1923-E1932.
• [74]Prufert K, Vogel A, Krohne G: The lamin CxxM motif promotes nuclear membrane growth. J Cell Sci 2004, 117:6105-6116.
• [75]Ralle T, Grund C, Franke WW, Stick R: Intranuclear membrane structure formations by CaaX-containing nuclear proteins. J Cell Sci 2004, 117:6095-6104.
• [76]Heng MY, Lin ST, Verret L, Huang Y, Kamiya S, Padiath QS, Tong Y, Palop JJ, Huang EJ, Ptacek LJ, Fu YH: Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model. J Clin Invest 2013, 123:2719-2729.
• [77]Malhas AN, Lee CF, Vaux DJ: Lamin B1 controls oxidative stress responses via Oct-1. J Cell Biol 2009, 184:45-55.
• [78]Columbaro M, Mattioli E, Maraldi NM, Ortolani M, Gasparini L, D’Apice MR, Postorivo D, Nardone AM, Avnet S, Cortelli P, et al.: Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. Biochim Biophys Acta 1832, 2013:411-420.
• [79]Xu N, Papagiannakopoulos T, Pan G, Thomson JA, Kosik KS: MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 2009, 137:647-658.
• [80]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297.
• [81]Esteller M: Non-coding RNAs in human disease. Nat Rev Genet 2011, 12:861-874.
• [82]Qureshi IA, Mehler MF: Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci 2012, 13:528-541.
• [83]Pauli A, Rinn JL, Schier AF: Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 2011, 12:136-149.
• [84]Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120:15-20.
• [85]Lau P, Verrier JD, Nielsen JA, Johnson KR, Notterpek L, Hudson LD: Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci 2008, 28:11720-11730.
• [86]Budde H, Schmitt S, Fitzner D, Opitz L, Salinas-Riester G, Simons M: Control of oligodendroglial cell number by the miR-17-92 cluster. Development 2010, 137:2127-2132.
• [87]Dugas JC, Cuellar TL, Scholze A, Ason B, Ibrahim A, Emery B, Zamanian JL, Foo LC, McManus MT, Barres BA: Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron 2010, 65:597-611.
• [88]Zhao X, He X, Han X, Yu Y, Ye F, Chen Y, Hoang T, Xu X, Mi QS, Xin M, et al.: MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 2010, 65:612-626.
• [89]Dugas JC, Notterpek L: MicroRNAs in oligodendrocyte and Schwann cell differentiation. Dev Neurosci 2011, 33:14-20.
• [90]Shin S, Cha HJ, Lee EM, Jung JH, Lee SJ, Park IC, Jin YW, An S: MicroRNAs are significantly influenced by p53 and radiation in HCT116 human colon carcinoma cells. Int J Oncol 2009, 34:1645-1652.
• [91]Lin ST, Huang Y, Zhang L, Heng MY, Ptacek LJ, Fu YH: MicroRNA-23a promotes myelination in the central nervous system. Proc Natl Acad Sci USA 2013, 110:17468-17473.
• [92]Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, et al.: Long noncoding RNAs with enhancer-like function in human cells. Cell 2010, 143:46-58.
• [93]Berndt JA, Kim JG, Tosic M, Kim C, Hudson LD: The transcriptional regulator Yin Yang 1 activates the myelin PLP gene. J Neurochem 2001, 77:935-942.
• [94]Mercer TR, Qureshi IA, Gokhan S, Dinger ME, Li G, Mattick JS, Mehler MF: Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. BMC Neurosci 2010, 11:14. BioMed Central Full Text
• [95]Inoue K, Osaka H, Sugiyama N, Kawanishi C, Onishi H, Nezu A, Kimura K, Yamada Y, Kosaka K: A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR. Am J Hum Genet 1996, 59:32-39.
• [96]Inoue K: PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Neurogenetics 2005, 6:1-16.
• [97]Bauer J, Bradl M, Klein M, Leisser M, Deckwerth TL, Wekerle H, Lassmann H: Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes. J Neuropathol Exp Neurol 2002, 61:12-22.