当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin.

Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin.

Abstract：

:Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gigaxonin reintroduction have not been tested in human GAN nerve cells. Here we report the derivation of induced pluripotent stem cells (iPSCs) from three GAN patients with different GAN mutations. Motor neurons differentiated from GAN iPSCs exhibit accumulation of neurofilament (NF-L) and peripherin (PRPH) protein and formation of PRPH aggregates, the key pathological phenotypes observed in patients. Introduction of gigaxonin either using a lentiviral vector or as a stable transgene resulted in normalization of NEFL and PRPH levels in GAN neurons and disappearance of PRPH aggregates. Importantly, overexpression of gigaxonin had no adverse effect on survival of GAN neurons, supporting the feasibility of gene replacement therapy. Our findings demonstrate that GAN iPSCs provide a novel model for studying human GAN neuropathologies and for the development and testing of new therapies in relevant cell types.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Johnson-Kerner BL,Ahmad FS,Diaz AG,Greene JP,Gray SJ,Samulski RJ,Chung WK,Van Coster R,Maertens P,Noggle SA,Henderson CE,Wichterle H

doi

10.1093/hmg/ddu556

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

1420-31

issue

5

eissn

0964-6906

issn

1460-2083

pii

ddu556

journal_volume

24

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Cloning of a human homologue of the Xenopus laevis APX gene from the ocular albinism type 1 critical region.

    abstract：:Ocular albinism type 1 (OA1) is an X-linked recessive disorder characterized by a major impairment of visual acuity, nystagmus, strabismus, photophobia and retinal hypopigmentation. From the analysis of patients carrying deletions and translocations involving the distal short arm of the X chromosome (Xp22.3) we have i...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.3.373

    authors： Schiaffino MV,Bassi MT,Rugarli EI,Renieri A,Galli L,Ballabio A

    更新日期：1995-03-01 00:00:00

  • Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.

    abstract：:A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw094

    authors： de la Hoya M,Soukarieh O,López-Perolio I,Vega A,Walker LC,van Ierland Y,Baralle D,Santamariña M,Lattimore V,Wijnen J,Whiley P,Blanco A,Raponi M,Hauke J,Wappenschmidt B,Becker A,Hansen TV,Behar R,Investigators K,Nied

    更新日期：2016-06-01 00:00:00

  • Neuronal pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice.

    abstract：:GM2 gangliosidoses are a group of lysosomal storage disorders which include Sandhoff disease and Tay-Sachs disease. Dysregulation of glutamate receptors has been recently postulated in the pathology of Sandhoff disease. Glutamate receptor association with neuronal pentraxins 1 and 2, and the neuronal pentraxin recepto...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw422

    authors： Hooper AWM,Alamilla JF,Venier RE,Gillespie DC,Igdoura SA

    更新日期：2017-02-15 00:00:00

  • Germinal and somatic mutations in the PKD2 gene of renal cysts in autosomal dominant polycystic kidney disease.

    abstract：:Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in one of three genes: PKD1 on chromosome 16 accounts for approximately 85% of cases whereas PKD2 on chromosome 4 accounts for approximately 15%. Mutations in the PKD3 gene are rare. All patients present with similar clinical phenotypes, and t...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/8.3.509

    authors： Koptides M,Hadjimichael C,Koupepidou P,Pierides A,Constantinou Deltas C

    更新日期：1999-03-01 00:00:00

  • A functional single nucleotide polymorphism in the core promoter region of CALM1 is associated with hip osteoarthritis in Japanese.

    abstract：:Osteoarthritis (OA), a common skeletal disease, is a leading cause of disability among the elderly populations. OA is characterized by gradual loss of articular cartilage, but the etiology and pathogenesis of OA are largely unknown. Epidemiological and genetic studies have demonstrated that genetic factors play an imp...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi093

    authors： Mototani H,Mabuchi A,Saito S,Fujioka M,Iida A,Takatori Y,Kotani A,Kubo T,Nakamura K,Sekine A,Murakami Y,Tsunoda T,Notoya K,Nakamura Y,Ikegawa S

    更新日期：2005-04-15 00:00:00

  • Structure and genomic sequence of the myotonic dystrophy (DM kinase) gene.

    abstract：:The mutation causing myotonic dystrophy (DM) has recently been identified as an unstable CTG trinucleotide repeat located in the 3' untranslated region of a gene encoding for a protein with putative serine-threonine protein kinase activity. In this report we present the genomic sequences of the human and murine DM kin...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.3.299

    authors： Mahadevan MS,Amemiya C,Jansen G,Sabourin L,Baird S,Neville CE,Wormskamp N,Segers B,Batzer M,Lamerdin J

    更新日期：1993-03-01 00:00:00

  • Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model.

    abstract：:Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints of existing models of tauopathy. In order to generate a more versatile m...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv336

    authors： Cook C,Kang SS,Carlomagno Y,Lin WL,Yue M,Kurti A,Shinohara M,Jansen-West K,Perkerson E,Castanedes-Casey M,Rousseau L,Phillips V,Bu G,Dickson DW,Petrucelli L,Fryer JD

    更新日期：2015-11-01 00:00:00

  • Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.

    abstract：:Spinal muscular atrophy (SMA) is a common pediatric neuromuscular disorder caused by insufficient levels of the survival of motor neuron (SMN) protein. Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddn156

    authors： Kariya S,Park GH,Maeno-Hikichi Y,Leykekhman O,Lutz C,Arkovitz MS,Landmesser LT,Monani UR

    更新日期：2008-08-15 00:00:00

  • Isolation and characterization of a novel gene encoding nuclear protein at a locus (D11S636) tightly linked to multiple endocrine neoplasia type 1 (MEN1).

    abstract：:To identify a gene responsible for multiple endocrine neoplasia type 1 (MEN1), we attempted to isolate potentially transcribable fragments from cosmid clones derived from a region on chromosome 11q13 where genetic linkage studies and analyses of loss of heterozygosity in MEN1-associated tumors have localized the MEN1 ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/3.3.465

    authors： Toda T,Iida A,Miwa T,Nakamura Y,Imai T

    更新日期：1994-03-01 00:00:00

  • Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy.

    abstract：:Proximal spinal muscular atrophy (SMA) is a common autosomal recessive childhood form of motor neuron disease. Previous studies have highlighted nerve- and muscle-specific events in SMA, including atrophy of muscle fibres and post-synaptic motor endplates, loss of lower motor neuron cell bodies and denervation of neur...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm367

    authors： Murray LM,Comley LH,Thomson D,Parkinson N,Talbot K,Gillingwater TH

    更新日期：2008-04-01 00:00:00

  • A novel mouse model for genetic variation in 10-formyltetrahydrofolate synthetase exhibits disturbed purine synthesis with impacts on pregnancy and embryonic development.

    abstract：:Genetic variants in one-carbon folate metabolism have been identified as risk factors for disease because they may impair the production or use of one-carbon folates required for nucleotide synthesis and methylation. p.R653Q (1958G>A) is a single-nucleotide polymorphism (SNP) in the 10-formyltetrahydrofolate (formylTH...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt223

    authors： Christensen KE,Deng L,Leung KY,Arning E,Bottiglieri T,Malysheva OV,Caudill MA,Krupenko NI,Greene ND,Jerome-Majewska L,MacKenzie RE,Rozen R

    更新日期：2013-09-15 00:00:00

  • Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes.

    abstract：:Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt015

    authors： Twigg SR,Babbs C,van den Elzen ME,Goriely A,Taylor S,McGowan SJ,Giannoulatou E,Lonie L,Ragoussis J,Sadighi Akha E,Knight SJ,Zechi-Ceide RM,Hoogeboom JA,Pober BR,Toriello HV,Wall SA,Rita Passos-Bueno M,Brunner HG,Mathi

    更新日期：2013-04-15 00:00:00

  • Inactivation of the mouse Magel2 gene results in growth abnormalities similar to Prader-Willi syndrome.

    abstract：:Prader-Willi syndrome (PWS) is an imprinted genetic obesity disorder characterized by abnormalities of growth and metabolism. Multiple mouse models with deficiency of one or more PWS candidate genes have partially correlated individual genes with aspects of the PWS phenotype, although the genetic origin of defects in ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm225

    authors： Bischof JM,Stewart CL,Wevrick R

    更新日期：2007-11-15 00:00:00

  • Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease.

    abstract：:Hirschsprung disease (HSCR) is a frequent neurocristopathy characterized by the absence of submucosal and myenteric plexuses in a variable length of the gastrointestinal tract. Pedigrees and segregation analyses suggested the involvement of one or several dominant genes with low penetrance in HSCR. Considering that RE...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.9.1449

    authors： Doray B,Salomon R,Amiel J,Pelet A,Touraine R,Billaud M,Attié T,Bachy B,Munnich A,Lyonnet S

    更新日期：1998-09-01 00:00:00

  • Mild Nijmegen breakage syndrome phenotype due to alternative splicing.

    abstract：:Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), characterized by microcephaly, chromosomal instability, radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin; however, 1...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi482

    authors： Varon R,Dutrannoy V,Weikert G,Tanzarella C,Antoccia A,Stöckl L,Spadoni E,Krüger LA,di Masi A,Sperling K,Digweed M,Maraschio P

    更新日期：2006-03-01 00:00:00

  • PAX genes: what's new in developmental biology and cancer?

    abstract：:PAX genes encode nuclear transcription factors which are rapidly becoming regarded as major controllers of developmental processes in both vertebrates and invertebrates. Mutations in murine Pax genes underlie three natural mouse alleles and two corresponding human syndromes. Murine Pax genes have been shown to be prot...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/4.suppl_1.1717

    authors： Stuart ET,Gruss P

    更新日期：1995-01-01 00:00:00

  • Rapid identification of gene sequences for transcriptional map assembly by direct cDNA screening of genomic reference libraries.

    abstract：:We have used the direct cDNA screening protocol to identify sequences transcribed in cerebral cortex from a reference library of human Xq28. To derive coding sequences from these genomic clones, we first identified fragments containing transcribed sequences and subjected these to exon trapping or to partial sequencing...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/3.11.2019

    authors： Lawrence BJ,Schwabe W,Kioschis P,Coy JF,Poustka A,Brennan MB,Hochgeschwender U

    更新日期：1994-11-01 00:00:00

  • Defective glucocorticoid hormone receptor signaling leads to increased stress and anxiety in a mouse model of Angelman syndrome.

    abstract：:Angelman syndrome (AS) is a neurodevelopmental disorder caused due to deletions or loss-of-function mutations in maternally inherited UBE3A. Ube3a functions as an ubiquitin ligase as well as a transcriptional coactivator of steroid hormone receptors. However, the mechanisms by which maternal Ube3a deficiency gives ris...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr614

    authors： Godavarthi SK,Dey P,Maheshwari M,Jana NR

    更新日期：2012-04-15 00:00:00

  • Point mutations at the carboxy terminus of the human dystrophin gene: implications for an association with mental retardation in DMD patients.

    abstract：:Duchenne and Becker muscular dystrophies (DMD/BMD) are caused by mutations in the human dystrophin gene. About two-thirds of DMD/BMD patients exhibit gross rearrangements in the gene whereas the mutations in the remaining one third are thought to be point mutations or minor structural lesions. By means of various prog...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.11.1877

    authors： Lenk U,Hanke R,Thiele H,Speer A

    更新日期：1993-11-01 00:00:00

  • Mapping of two genes encoding isoforms of the actin binding protein ABP-280, a dystrophin like protein, to Xq28 and to chromosome 7.

    abstract：:ABP-280 is a ubiquitous actin binding protein present in the cytoskeleton of many different cell types. ABP-280 was mapped to distal Xq28, 50-60 kb downstream of the Green Colour Pigment (GCP) genes. To establish if ABP-280 may be a candidate for one of the muscle disease localized by linkage analysis to distal Xq28 w...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.6.761

    authors： Maestrini E,Patrosso C,Mancini M,Rivella S,Rocchi M,Repetto M,Villa A,Frattini A,Zoppè M,Vezzoni P

    更新日期：1993-06-01 00:00:00

  • Identification and analysis of large intergenic non-coding RNAs regulated by p53 family members through a genome-wide analysis of p53-binding sites.

    abstract：:p53 is one of the most important known tumor suppressor genes, and it is inactivated in approximately half of human cancers. p53 family members execute various functions, such as apoptosis induction and cell cycle arrest, by modulating transcriptional regulation. Therefore, the direct transcriptional targets of the p5...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt673

    authors： Idogawa M,Ohashi T,Sasaki Y,Maruyama R,Kashima L,Suzuki H,Tokino T

    更新日期：2014-06-01 00:00:00

  • Mapping the Von Hippel-Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis.

    abstract：:Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome in which affected individuals have a greatly increased predisposition to the development of haemangioblastomas of the central nervous system and retina, renal cell carcinoma and phaeochromocytoma. The VHL gene has been mapped to chromos...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.7.879

    authors： Richards FM,Phipps ME,Latif F,Yao M,Crossey PA,Foster K,Linehan WM,Affara NA,Lerman MI,Zbar B

    更新日期：1993-07-01 00:00:00

  • The genetic and metabolic signature of oncocytic transformation implicates HIF1alpha destabilization.

    abstract：:We previously showed that disruptive complex I mutations in mitochondrial DNA are the main genetic hallmark of oncocytic tumors of the thyroid and kidney. We here report a high frequency of homoplasmic disruptive mutations in a large panel of oncocytic pituitary and head-and-neck tumors. The presence of such mutations...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp566

    authors： Porcelli AM,Ghelli A,Ceccarelli C,Lang M,Cenacchi G,Capristo M,Pennisi LF,Morra I,Ciccarelli E,Melcarne A,Bartoletti-Stella A,Salfi N,Tallini G,Martinuzzi A,Carelli V,Attimonelli M,Rugolo M,Romeo G,Gasparre G

    更新日期：2010-03-15 00:00:00

  • Investigating the genetic association between ERAP1 and ankylosing spondylitis.

    abstract：:A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conduc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp371

    authors： Harvey D,Pointon JJ,Evans DM,Karaderi T,Farrar C,Appleton LH,Sturrock RD,Stone MA,Oppermann U,Brown MA,Wordsworth BP

    更新日期：2009-11-01 00:00:00

  • Interactome analysis reveals that FAM161A, deficient in recessive retinitis pigmentosa, is a component of the Golgi-centrosomal network.

    abstract：:Defects in FAM161A, a protein of unknown function localized at the cilium of retinal photoreceptor cells, cause retinitis pigmentosa, a form of hereditary blindness. By using different fragments of this protein as baits to screen cDNA libraries of human and bovine retinas, we defined a yeast two-hybrid-based FAM161A i...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv085

    authors： Di Gioia SA,Farinelli P,Letteboer SJ,Arsenijevic Y,Sharon D,Roepman R,Rivolta C

    更新日期：2015-06-15 00:00:00

  • Functional characterization of SIM1-associated enhancers.

    abstract：:Haploinsufficiency of the single-minded homology 1 (SIM1) gene in humans and mice leads to severe obesity, suggesting that altered expression of SIM1, by way of regulatory elements such as enhancers, could predispose individuals to obesity. Here, we identified transcriptional enhancers that could regulate SIM1, using ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt559

    authors： Kim MJ,Oksenberg N,Hoffmann TJ,Vaisse C,Ahituv N

    更新日期：2014-04-01 00:00:00

  • Large-scale analysis of exonized mammalian-wide interspersed repeats in primate genomes.

    abstract：:Transposable elements (TEs) are major sources of new exons in higher eukaryotes. Almost half of the human genome is derived from TEs, and many types of TEs have the potential to exonize. In this work, we conducted a large-scale analysis of human exons derived from mammalian-wide interspersed repeats (MIRs), a class of...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp152

    authors： Lin L,Jiang P,Shen S,Sato S,Davidson BL,Xing Y

    更新日期：2009-06-15 00:00:00

  • A tandem repeat array in IG-DMR is essential for imprinting of paternal allele at the Dlk1-Dio3 domain during embryonic development.

    abstract：:Genomic imprinting is a phenomenon that causes parent-origin-specific monoallelic expression of a small subset of genes, known as imprinted genes, by parentally inherited epigenetic marks. Imprinted genes at the delta-like homolog 1 gene (Dlk1)-type III iodothyronine deiodinase gene (Dio3) imprinted domain, regulated ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy235

    authors： Saito T,Hara S,Kato T,Tamano M,Muramatsu A,Asahara H,Takada S

    更新日期：2018-09-15 00:00:00

  • Modifier genes and non-genetic factors reshape anatomical deficits in Zfp423-deficient mice.

    abstract：:Development of neural circuitry depends on the integration of signaling pathways to coordinate specification, proliferation and differentiation of cell types in the right number, in the right place, at the right time. Zinc finger protein 423 (Zfp423), a 30-zinc finger transcription factor, forms alternate complexes wi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr300

    authors： Alcaraz WA,Chen E,Valdes P,Kim E,Lo YH,Vo J,Hamilton BA

    更新日期：2011-10-01 00:00:00

  • Genome editing strategies for fetal hemoglobin induction in beta-hemoglobinopathies.

    abstract：:Genome editing to correct a defective β-globin gene or induce fetal globin (HbF) for patients with beta-hemoglobinopathies has the potential to be a curative strategy available to all. HbF reactivation has long been an area of intense interest given the HbF inhibition of sickle hemoglobin (HbS) polymerization. Patient...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa088

    authors： Demirci S,Leonard A,Tisdale JF

    更新日期：2020-09-30 00:00:00