当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > A point mutation in the neu-1 locus causes the neuraminidase defect in the SM/J mouse.

A point mutation in the neu-1 locus causes the neuraminidase defect in the SM/J mouse.

Abstract：

:Lysosomal neuraminidase (sialidase) occurs in a high molecular weight complex with the glycosidase beta-galactosidase and the serine carboxypeptidase protective protein/cathepsin A (PPCA). Association of the enzyme with PPCA is crucial for its correct targeting and lysosomal activation. In man two genetically distinct storage disorders are associated with either a primary or a secondary deficiency of lysosomal neuraminidase: sialidosis and galactosialidosis. In the mouse the naturally occurring inbred strain SM/J presents with a number of phenotypic abnormalities that have been attributed to reduced neuraminidase activity. SM/J mice were originally characterized by their altered sialylation of several lysosomal glycoproteins. This defect was linked to a single gene, neu-1 , on chromosome 17, which was mapped by linkage analysis to the H-2 locus. In addition, these mice have an altered immune response that has also been coupled to a deficiency of the Neu-1 neuraminidase. Here we report the identification in SM/J mice of a single amino acid substitution (L209I) in the Neu-1 protein which is responsible for the partial deficiency of lysosomal neuraminidase. We propose that the reduced activity is caused by the enzyme's altered affinity for its substrate, rather than a change in substrate specificity or turnover rate. The mutant enzyme is correctly compartmentalized in lysosomes and maintains the ability to associate with its activating protein, PPCA. We propose that it is this mutation that is responsible for the SM/J phenotype.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Rottier RJ,Bonten E,d'Azzo A

doi

10.1093/hmg/7.2.313

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

313-21

issue

2

eissn

0964-6906

issn

1460-2083

pii

ddb029

journal_volume

7

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

    abstract：:Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.9.1283

    authors： Sukegawa K,Nakamura H,Kato Z,Tomatsu S,Montaño AM,Fukao T,Toietta G,Tortora P,Orii T,Kondo N

    更新日期：2000-05-22 00:00:00

  • Identification and developmental expression of the Xenopus laevis cystic fibrosis transmembrane conductance regulator gene.

    abstract：:An amphibian homologue of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene has been isolated from Xenopus laevis by polymerase chain reaction (PCR) amplification. The 4455bp sequence encodes a predicted polypeptide of 1485 amino acids which has an overall homology at the amino acid level of 77...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/1.2.77

    authors： Tucker SJ,Tannahill D,Higgins CF

    更新日期：1992-05-01 00:00:00

  • Huntingtin affinity for partners is not changed by polyglutamine length: aggregation itself triggers aberrant interactions.

    abstract：:Huntington's disease (HD) is caused by the expansion mutation above a length threshold of a polyglutamine (polyQ) stretch in the huntingtin (Htt) protein. Mutant Htt (mHtt) pathogenicity is proposed to rely on its malfunction and propensity to misfold and aggregate. Htt has scaffolding properties and has been reported...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr178

    authors： Davranche A,Aviolat H,Zeder-Lutz G,Busso D,Altschuh D,Trottier Y,Klein FA

    更新日期：2011-07-15 00:00:00

  • Association of prolactin receptor (PRLR) variants with prolactinomas.

    abstract：:Prolactinomas are the most frequent type of pituitary tumors, which represent 10-20% of all intracranial neoplasms in humans. Prolactinomas develop in mice lacking the prolactin receptor (PRLR), which is a member of the cytokine receptor superfamily that signals via Janus kinase-2-signal transducer and activator of tr...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy396

    authors： Gorvin CM,Newey PJ,Rogers A,Stokes V,Neville MJ,Lines KE,Ntali G,Lees P,Morrison PJ,Singhellakis PN,Malandrinou FC,Karavitaki N,Grossman AB,Karpe F,Thakker RV

    更新日期：2019-03-15 00:00:00

  • Identification of disease genes by whole genome CGH arrays.

    abstract：:Small, submicroscopic, genomic deletions and duplications (1 kb to 10 Mb) constitute up to 15% of all mutations underlying human monogenic diseases. Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicrosco...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddi268

    authors： Vissers LE,Veltman JA,van Kessel AG,Brunner HG

    更新日期：2005-10-15 00:00:00

  • Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis.

    abstract：:Lysosomal neuraminidase is the key enzyme for the intralysosomal catabolism of sialylated glycoconjugates and is deficient in two neurodegenerative lysosomal disorders, sialidosis and galactosialidosis. Here we report the identification of eight novel mutations in the neuraminidase gene of 11 sialidosis patients with ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.18.2715

    authors： Bonten EJ,Arts WF,Beck M,Covanis A,Donati MA,Parini R,Zammarchi E,d'Azzo A

    更新日期：2000-11-01 00:00:00

  • Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation.

    abstract：:Progressive myoclonus epilepsy of Lafora type (LD, MIM 254780) is a fatal autosomal recessive disorder characterized by the presence of progressive neurological deterioration, myoclonus, epilepsy and polyglucosan intracellular inclusion bodies, called Lafora bodies. Lafora bodies resemble glycogen with reduced branchi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg340

    authors： Fernández-Sánchez ME,Criado-García O,Heath KE,García-Fojeda B,Medraño-Fernández I,Gomez-Garre P,Sanz P,Serratosa JM,Rodríguez de Córdoba S

    更新日期：2003-12-01 00:00:00

  • Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice.

    abstract：:Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine (polyQ) tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu522

    authors： Kurosawa M,Matsumoto G,Kino Y,Okuno M,Kurosawa-Yamada M,Washizu C,Taniguchi H,Nakaso K,Yanagawa T,Warabi E,Shimogori T,Sakurai T,Hattori N,Nukina N

    更新日期：2015-02-15 00:00:00

  • Saturation multipoint linkage mapping of chromosome 6q in type 1 diabetes.

    abstract：:Linkage analysis of type 1 diabetes sib pair families (n = 334) has suggested two separate regions of human chromosome 6q are linked to disease (designated IDDM5 and IDDM8). To test if these are false positive results, all available sib pair families (n = 429) were typed using a 92% informative map of chromosome 6q an...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/5.7.1071

    authors： Davies JL,Cucca F,Goy JV,Atta ZA,Merriman ME,Wilson A,Barnett AH,Bain SC,Todd JA

    更新日期：1996-07-01 00:00:00

  • Comparative genome analysis delimits a chromosomal domain and identifies key regulatory elements in the alpha globin cluster.

    abstract：:We have cloned, sequenced and annotated segments of DNA spanning the mouse, chicken and pufferfish alpha globin gene clusters and compared them with the corresponding region in man. This has defined a small segment ( approximately 135-155 kb) of synteny and conserved gene order, which may contain all of the elements r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.4.371

    authors： Flint J,Tufarelli C,Peden J,Clark K,Daniels RJ,Hardison R,Miller W,Philipsen S,Tan-Un KC,McMorrow T,Frampton J,Alter BP,Frischauf AM,Higgs DR

    更新日期：2001-02-15 00:00:00

  • A mouse model of Angelman syndrome imprinting defects.

    abstract：:Angelman syndrome, Prader-Will syndrome and Dup15q syndrome map to a cluster of imprinted genes located at 15q11-q13. Imprinting at this domain is regulated by an imprinting control region consisting of two distinct elements, the Angelman syndrome imprinting center (AS-IC) and the Prader-Willi syndrome imprinting cent...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy345

    authors： Lewis MW,Vargas-Franco D,Morse DA,Resnick JL

    更新日期：2019-01-15 00:00:00

  • Secondary BH4 deficiency links protein homeostasis to regulation of phenylalanine metabolism.

    abstract：:Metabolic control of phenylalanine concentrations in body fluids is essential for cognitive development and executive function. The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy079

    authors： Eichinger A,Danecka MK,Möglich T,Borsch J,Woidy M,Büttner L,Muntau AC,Gersting SW

    更新日期：2018-05-15 00:00:00

  • Big data collision: the internet of things, wearable devices and genomics in the study of neurological traits and disease.

    abstract：:Advances in information technology (IT) hardware in the last decade have led to the advent of small connected devices broadly referred to as the Internet of Things (IoT). The IoT and its subcategory of wearable devices (wearables) both have the potential to greatly impact biomedical research. This focused review cover...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy092

    authors： Talboom JS,Huentelman MJ

    更新日期：2018-05-01 00:00:00

  • Co-expression of mutated and normal adrenoleukodystrophy protein reduces protein function: implications for gene therapy of X-linked adrenoleukodystrophy.

    abstract：:Inherited defects in the X-chromosomal adrenoleukodystrophy (ALD; ABCD1) gene are the genetic cause of the severe neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). Biochemically the accumulation of very long-chain fatty acids, caused by impaired peroxisomal beta-oxidation, is the pathognomonic characte...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.18.2609

    authors： Unterrainer G,Molzer B,Forss-Petter S,Berger J

    更新日期：2000-11-01 00:00:00

  • Chromosome fragility and the abnormal replication of the FMR1 locus in fragile X syndrome.

    abstract：:Fragile X Syndrome (FXS) is a learning disability seen in individuals who have >200 CGG•CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu006

    authors： Yudkin D,Hayward BE,Aladjem MI,Kumari D,Usdin K

    更新日期：2014-06-01 00:00:00

  • Characterization of myotonic dystrophy kinase (DMK) protein in human and rodent muscle and central nervous tissue.

    abstract：:Myotonic dystrophy (DM) is the most common form of inherited neuromuscular disease in adults and is characterized by progressive muscle wasting and myotonia. The mutation responsible for DM has been identified as the amplification of a polymorphic (CTG)n repeat in the 3' untranslated region of a gene encoding a serine...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.6.1063

    authors： Whiting EJ,Waring JD,Tamai K,Somerville MJ,Hincke M,Staines WA,Ikeda JE,Korneluk RG

    更新日期：1995-06-01 00:00:00

  • Convergent linkage evidence from two Latin-American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34.

    abstract：:We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the cl...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl254

    authors： Herzberg I,Jasinska A,García J,Jawaheer D,Service S,Kremeyer B,Duque C,Parra MV,Vega J,Ortiz D,Carvajal L,Polanco G,Restrepo GJ,López C,Palacio C,Levinson M,Aldana I,Mathews C,Davanzo P,Molina J,Fournier E,Bejar

    更新日期：2006-11-01 00:00:00

  • Formation of polyglutamine inclusions in non-CNS tissue.

    abstract：:Huntington's disease (HD) is one of a class of inherited progressive neurodegenerative disorders that are caused by a CAG/polyglutamine repeat expansion. We have previously generated mice that are transgenic for exon 1 of the HD gene carrying highly expanded CAG repeats which develop a progressive movement disorder an...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/8.5.813

    authors： Sathasivam K,Hobbs C,Turmaine M,Mangiarini L,Mahal A,Bertaux F,Wanker EE,Doherty P,Davies SW,Bates GP

    更新日期：1999-05-01 00:00:00

  • Protein kinase C gamma, a protein causative for dominant ataxia, negatively regulates nuclear import of recessive-ataxia-related aprataxin.

    abstract：:Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disease caused by mutations in the gene encoding protein kinase C gamma (PKC gamma). We report an SCA14 family with a novel deletion of a termination-codon-containing region, resulting in a missense change and a C-terminal 13-amino-acid extension with inc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp298

    authors： Asai H,Hirano M,Shimada K,Kiriyama T,Furiya Y,Ikeda M,Iwamoto T,Mori T,Nishinaka K,Konishi N,Udaka F,Ueno S

    更新日期：2009-10-01 00:00:00

  • Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.

    abstract：:Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to s...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.1.93

    authors： Sankila EM,Pakarinen L,Kääriäinen H,Aittomäki K,Karjalainen S,Sistonen P,de la Chapelle A

    更新日期：1995-01-01 00:00:00

  • C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity.

    abstract：:P/Q-type voltage-gated calcium channels are regulated, in part, through the cytoplasmic C-terminus of their alpha1A subunit. Genetic absence or alteration of the C-terminus leads to abnormal channel function and neurological disease. Here, we show that the terminal 60-75 kDa of the endogenous alpha1A C-terminus is cle...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl080

    authors： Kordasiewicz HB,Thompson RM,Clark HB,Gomez CM

    更新日期：2006-05-15 00:00:00

  • The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies.

    abstract：:To enhance our understanding of the autosomal recessive limb-girdle muscular dystrophy (LGMD), patients from six genetically distinct forms (LGMD2A to LGMD2F) were studied with antibodies directed against four sarcoglycan subunits (alpha-, beta-, gamma-, delta-SG), dystrophin, beta-dystroglycan (beta-DG) and merosin. ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/5.12.1963

    authors： Vainzof M,Passos-Bueno MR,Canovas M,Moreira ES,Pavanello RC,Marie SK,Anderson LV,Bonnemann CG,McNally EM,Nigro V,Kunkel LM,Zatz M

    更新日期：1996-12-01 00:00:00

  • Hypermorphic and hypomorphic AARS alleles in patients with CMT2N expand clinical and molecular heterogeneities.

    abstract：:Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes implicated in several dominant and recessive disease phenotypes. The canonical function of ARSs is to couple an amino acid to a cognate transfer RNA (tRNA). We identified three novel disease-associated missense mutations in the alanyl-tRNA synthetase...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy290

    authors： Weterman MAJ,Kuo M,Kenter SB,Gordillo S,Karjosukarso DW,Takase R,Bronk M,Oprescu S,van Ruissen F,Witteveen RJW,Bienfait HME,Breuning M,Verhamme C,Hou YM,de Visser M,Antonellis A,Baas F

    更新日期：2018-12-01 00:00:00

  • Prenylated retinal ciliopathy protein RPGR interacts with PDE6δ and regulates ciliary localization of Joubert syndrome-associated protein INPP5E.

    abstract：:Ciliary trafficking defects underlie the pathogenesis of severe human ciliopathies, including Joubert Syndrome (JBTS), Bardet-Biedl Syndrome, and some forms of retinitis pigmentosa (RP). Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are common causes of RP-associated photoreceptor degen...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw281

    authors： Rao KN,Zhang W,Li L,Anand M,Khanna H

    更新日期：2016-10-15 00:00:00

  • Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates.

    abstract：:Expansion of a polyglutamine tract in ataxin-3 (AT3) results in spinocerebellar ataxia type 3/Machado-Joseph disease, one of the nine polyglutamine neurodegenerative diseases. Understanding the normal functions of AT3 as well as its function in the context of expansion of the polyglutamine tract is critical for unders...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl164

    authors： Zhong X,Pittman RN

    更新日期：2006-08-15 00:00:00

  • Characterization of four mutations in the neurofibromatosis type 1 gene by denaturing gradient gel electrophoresis (DGGE).

    abstract：:Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders. The gene responsible for the disease has a very high mutation rate, approximately fifty per cent of NF1 patients appear to have a de novo mutation. The search for mutations is hampered by the large size of the NF1 gene and up to date, relati...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/3.4.639

    authors： Valero MC,Velasco E,Moreno F,Hernández-Chico C

    更新日期：1994-04-01 00:00:00

  • Inhibition of death-associated protein kinase 1 attenuates the phosphorylation and amyloidogenic processing of amyloid precursor protein.

    abstract：:Extracellular deposition of amyloid-beta (Aβ) peptide, a metabolite of sequential cleavage of amyloid precursor protein (APP), is a critical step in the pathogenesis of Alzheimer's disease (AD). While death-associated protein kinase 1 (DAPK1) is highly expressed in AD brains and its genetic variants are linked to AD r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw114

    authors： Kim BM,You MH,Chen CH,Suh J,Tanzi RE,Ho Lee T

    更新日期：2016-06-15 00:00:00

  • Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts.

    abstract：:Mutations in the MLC1 gene are responsible for one form of the neurological disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC). The disease is a type of vacuolating myelinopathy. The biochemical properties and the function of the MLC1 protein are unknown. To characterize MLC1, we generated polyc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh291

    authors： Teijido O,Martínez A,Pusch M,Zorzano A,Soriano E,Del Río JA,Palacín M,Estévez R

    更新日期：2004-11-01 00:00:00

  • Functional implications of splicing polymorphisms in the human genome.

    abstract：:Proper splicing is often crucial for gene functioning and its disruption may be strongly deleterious. Nevertheless, even the essential for splicing canonical dinucleotides of the splice sites are often polymorphic. Here, we use data from The 1000 Genomes Project to study single-nucleotide polymorphisms (SNPs) in the c...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt200

    authors： Kurmangaliyev YZ,Sutormin RA,Naumenko SA,Bazykin GA,Gelfand MS

    更新日期：2013-09-01 00:00:00

  • Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice.

    abstract：:Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of A beta deposits. In the present study, we asked whether elevating the levels of Apo E can, in a dominant fashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via the mouse prion prote...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.22.2525

    authors： Lesuisse C,Xu G,Anderson J,Wong M,Jankowsky J,Holtz G,Gonzalez V,Wong PC,Price DL,Tang F,Wagner S,Borchelt DR

    更新日期：2001-10-15 00:00:00