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1.
In the search for candidate genes for the tuberous sclerosis (TSC1) disease locus on chromosome 9q34, we have isolated an overlapping series of 22 plasmid and phage cDNA clones covering nearly 7 kb and with an open reading frame of 5070 bp encoding a protein of 1690 amino acids. The putative protein product is a member of the kinesin superfamily and is homologous to the mouse KIF1A and theCaenorhabditas elegansunc-104 genes. Both KIF1A and unc-104 function in the anterograde axonal transport of synaptic vesicles. The human homolog is therefore termed H-ATSV (axonal transporter of synaptic vesicles, HGMW-approved nomenclature ATSV) Screening of DNA from 107 tuberous sclerosis patients and 80 unaffected individuals with H-ATSV cDNA probes by pulsed-field gel electrophoresis/Southern blotting following digestion by rare-cutting methylation-sensitive restriction enzymes showed variant banding patterns in three patients with tuberous sclerosis. However, further analysis indicated that these variant fragments represent a rare polymorphism probably associated with methylation of clustered restriction sites. There is no evidence to support H-ATSV as a candidate gene for TSC1. 相似文献
2.
Axonal and dendritic transport in single Purkinje neurons of cerebellar slice cultures was quantified as single transport
distances. Examination of the cells within a vital tissue was regarded as being an approach to the in situ condition. The
Purkinje cells were organotypically integrated in the in vitro tissues and extended long axonal projections connecting synapses
to the target neurons. The tracer horseradish peroxidase (HRP) was applied via microinjection to the somata of the Purkinje
cells and the injected neurons were incubated thereafter for defined time-intervals. The tracer was transported anterogradely
into the neuron processes. The measurements on both the axonal and the dendritic transport of microinjected HRP revealed continuous
transportation with increasing times of postincubation. This transport was reduced by the use of microtubule-depolymerizing
drugs. The axonal transport of the tracer was either retarded in colchicine-treated cells or continuously reduced for up to
50% in vinblastine-treated neurons. Thus, a correlation of axonal transport to the microtubules was demonstrated. The dendrites
were filled with the tracer after 60 min of postincubation. Dendritic transport was reduced by the use of vinblastine, and
not significantly by colchicine. The results strongly support the dependence of neuronal transport on microtubules as a component
of the cytoskeleton.
Received: 26 April 1998 / Accepted: 18 August 1998 相似文献
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René F.M. de Coo Paul A.L. Buddiger Hubert J.M. Smeets Bernard A. van Oost 《Mammalian genome》1999,10(1):49-53
The genomic organization of the human 51-kDa subunit gene (NDUFV1) on human Chromosome (Chr) 11q13 was determined. The NDUFV1
gene consists of 10 exons. Exon 1 encodes for the 20-amino-acids-long import sequence, and exon 1 through 10 codes for the
444-amino-acids-long mature protein. The protein sequence is highly conserved between human and bovine. Northern blotting
analysis showed that the NDUFV1 gene expression varies widely among tissues and that in testis a unique mRNA species is present.
In comparison with the other complex I flavoproteins, the expression of the 51-kDa gene in pancreatic tissue is high.
Received: 5 May 1998 / Accepted: 28 August 1998 相似文献
5.
Congenital atrichia is a rare autosomal recessive disorder of hair development, characterized by complete loss of hair shortly
after birth. Evidence of linkage to chromosome 8p12 has been established, implicating the human homolog of the mouse hairless
(hr) gene as a candidate gene. We have previously identified missense mutations in families with congenital atrichia. Here,
we report the first deletion mutation (2147del C) in exon 9 of the human hairless gene leading to a frameshift and downstream
premature termination codon in five Palestinian families of Arab origin.
Received: 31 July 1998 / Accepted: 31 August 1998 相似文献
6.
New insights into porcine-human synteny conservation 总被引:1,自引:0,他引:1
Niels J. Larsen Stefan Marklund Kemba A. Kelly Massoud Malek Christopher K. Tuggle Martine Yerle Max F. Rothschild 《Mammalian genome》1999,10(5):488-491
Eleven genes were mapped to the porcine genome with the aim of improving the human-porcine comparative gene map. Five of
these genes were from regions of the human genome painted by porcine chromosomal probes; of these, two mapped to chromosomes
not expected from the painting results. Among the six genes from human regions not painted by porcine chromosomal probes,
three genes did not map where expected by the principle of parsimony. Several of the gene assignments indicate the existence
of small regions of conserved synteny not detected by heterologous chromosome painting, especially in telomeric regions. We
have also detected new rearrangements in gene order within the regions of correspondence between human Chromosome (HSA) 15
and porcine Chromosome (SSC) 1 as well as between HSA4 and SSC8.
Received: 30 September 1998 / Accepted: 3 December 1998 相似文献
7.
Dimitri Pirottin Dominique Poncelet Luc Grobet Luis José Royo Benoit Brouwers Julio Masabanda Haruko Takeda Ruedi Fries Yoshikazu Sugimoto James E. Womack Susana Dunner Michel Georges 《Mammalian genome》1999,10(3):289-293
A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding
to YAC ends. The contig comprises 27 YACs, has an average depth of 4.3 YACs, and spans an estimated 1.2 Mb. A linkage map
was constructed based on five of the microsatellite markers anchored to the contig and shown to span 7 cM, yielding a ratio
of 160 kb/1 cM for the corresponding chromosome region. Comparative mapping data indicate that the constructed contig spans
an evolutionary breakpoint connecting two chromosome segments that are syntenic but not adjacent in the human. Consolidation
of human gene order by means of whole genome radiation hybrids and its comparison with the bovine order as inferred from the
contig confirm conservation of gene order within segments.
Received: 6 August 1998 / Accepted: 28 October 1998 相似文献
8.
Dystonia musculorum (dt) is a recessive hereditary neuropathy of the mouse. Affected animals display loss of limb coordination and twisting of the trunk. Sensory nerve fibers of these mice are severely reduced in number, and the remaining fibers present numerous axonal swellings. The gene defective in dt, dystonin (Dst), encodes a cytoskeletal linker protein that forms the bridge between F-actin and intermediate filaments. Dst is expressed during embryogenesis, whereas overt phenotype in dt mice only appears during the second week after birth. Here we show that axonal swellings are present in sensory nerve fibers of dt embryos as early as E15.5, before myelination and radial axonal growth have begun. Thus disease progression is gradual in dt mice, having begun during embryogenesis. In dt embryos, microtubule network disorganization and cytoplasmic organelle accumulation within axonal swellings were consistently observed. In addition, a few of the axonal swellings presented intermediate filament accumulation. These results demonstrate that dystonin is required for cytoskeleton organization during axonogenesis. They also suggest that axonal transport defects, through microtubule network perturbation, may be the primary mechanism of neurodegeneration in dt mice. Dev. Genet. 22:160–168, 1998. © 1998 Wiley-Liss, Inc. 相似文献
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J. E. Tucker R. J. Winkfein S. K. Murthy J. S. Friedman M. A. Walter D. J. Demetrick P. P. M. Schnetkamp 《Human genetics》1998,103(4):411-414
The retinal rod Na-Ca+K exchanger is a unique calcium extrusion protein found only in the outer segments of retinal rod photoreceptors.
Rod Na-Ca+K exchanger cDNA (NCKX1) has been cloned from bovine and human retinas. Here, we have used fluorescent in situ hybridization
and radiation hybrid mapping to localize the human NCKX1 gene to chromosome 15q22. We have determined the genomic organization
of human rod NCKX1 and found one intron in the 5’ untranslated region and eight introns within the coding region.
Received: 9 June 1998 / Accepted: 24 July 1998 相似文献
12.
Susannah M. Walpole Nathalie Ronce Celene Grayson Benoît Dessay John R. W. Yates D. Trump Annick Toutain 《Human genetics》1999,104(5):410-411
Nance-Horan syndrome (NHS) is an X-linked condition characterised by congenital cataracts, microphthalmia and/or microcornea,
unusual dental morphology, dysmorphic facial features, and developmental delay in some cases. Recent linkage studies have
mapped the NHS disease gene to a 3.5-cM interval on Xp22.2 between DXS1053 and DXS443. We previously identified a human homologue
of a mouse retinoic-acid-induced gene (RAI2) within the NHS critical flanking interval and have tested the gene as a candidate for Nance-Horan syndrome in nine NHS-affected
families. Direct sequencing of the RAI2 gene and predicted promoter region has revealed no mutations in the families screened; RAI2 is therefore unlikely to be associated with NHS.
Received: 11 December 1998 / Accepted: 1 March 1998 相似文献
13.
Noriko Esumi Marcia Budarf Lawrence Ciccarelli Beatrice Sellinger Christine A. Kozak Graeme Wistow 《Mammalian genome》1998,9(9):753-757
Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are small proteins, which are related both
by sequence and by in vitro enzyme activity. Here we show that the gene for DDT in human and mouse is identical in exon structure
to MIF. Both genes have two introns that are located at equivalent positions, relative to a twofold repeat in protein structure.
Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this
superfamily exist in nematodes and a plant, and a related gene in C. elegans shares an intron position with MIF and DDT. In addition to similarities in structure, the genes for DDT and MIF are closely
linked on human Chromosome (Chr) 22 and mouse Chr 10.
Received: 12 February 1998 / Accepted: 8 May 1998 相似文献
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The gracile axonal dystrophy (gad) mouse, which shows hereditary sensory ataxia and motor paresis, has been morphologically characterized by the dying back type of axonal degeneration in the nerve terminals of dorsal root ganglion cells and motor neurons. In the present study, using an intraspecific backcross between gad and C57BL/6J mice, the gracile axonal dystrophy (gad) gene was mapped to a region between D5Mit197 and D5Mit113. Estimated distances between gad and D5Mit197 and between gad and D5Mit113 are 0.4 ± 0.3 and 5.0 ± 1.0 cM, respectively. The gene order was defined: centromere- D5Mit81-D5Mit233-D5Mit184/D5Mit254-D5Mit256-D5Mit197-gad-D5Mit113-D5Mit7 . The mouse map location of the gad locus appears to be in a region homologous to human 4p15-p16. Our present data suggest that the nearest flanking marker D5Mit197 provides a useful anchor for the isolation of the gad gene in a yeast artificial chromosome contig. 相似文献
16.
Swetha Gowrishankar Lila Lyons Nisha Mohd Rafiq Agnes Roczniak-Ferguson Pietro De Camilli Shawn M. Ferguson 《Molecular biology of the cell》2021,32(11):1094
The dependence of neurons on microtubule-based motors for the movement of lysosomes over long distances raises questions about adaptations that allow neurons to meet these demands. Recently, JIP3/MAPK8IP3, a neuronally enriched putative adaptor between lysosomes and motors, was identified as a critical regulator of axonal lysosome abundance. In this study, we establish a human induced pluripotent stem cell (iPSC)-derived neuron model for the investigation of axonal lysosome transport and maturation and show that loss of JIP3 results in the accumulation of axonal lysosomes and the Alzheimer’s disease–related amyloid precursor protein (APP)-derived Aβ42 peptide. We furthermore reveal an overlapping role of the homologous JIP4 gene in lysosome axonal transport. These results establish a cellular model for investigating the relationship between lysosome axonal transport and amyloidogenic APP processing and more broadly demonstrate the utility of human iPSC–derived neurons for the investigation of neuronal cell biology and pathology. 相似文献
17.
Stephanie Henry Karl H. Pfenninger Justin L. Mott A.-C. Granholm 《Cell and tissue research》1999,297(1):67-79
Recent studies have implicated glycoconjugates on the membrane of growth cones as the necessary markers and intermediaries
for axonal recognition, axonal motility, and pathway development. One such glycoconjugate, glycoprotein 93 (gp93), has been
characterized, but the relative distribution of gp93 has yet to be described for the embryonic brain. In this study, the anatomical
distribution of gp93 has been analyzed at embryonic day 15 (E15) and E18, and on postnatal day 3 in the rat by using a polyclonal
gp93 antibody. Furthermore, fetal brain tissue transplanted into the adult rat eye has been tested for gp93 immunoreactivity,
since central noradrenergic neurons in brainstem transplants are known to provide a continuous source of growing axons, even
in adult tissue. In general, a greater abundance of gp93 immunoreactivity is apparent in the earlier embryonic stages (E15
and E18), whereas less is seen in the postnatal brain. The regions showing unique dispersal patterns of gp93 are the neuroepithelium,
cerebral cortex, septo-hippocampal pathways, brainstem, and midbrain. This study has therefore focused on these areas and
found implications for gp93 distribution appearing in the early development of specific neuronal pathways. Moreover, axons
stain densely for gp93 within brain tissue transplants. The presence of gp93 in areas of extensive axonal outgrowth in the
normal brain and in transplants suggests that this antibody is used as an early marker for axonal growth. Furthermore, gp93
might be used to map normal development in order to improve our understanding of diseases arising from developmental abnormalities.
Received: 17 June 1998 / Accepted: 23 November 1998 相似文献
18.
†Seiji Hitoshi Naoya Kojima †Susumu Kusunoki ‡Jin-ichi Inokuchi †Ichiro Kanazawa Shuichi Tsuji 《Journal of neurochemistry》1996,66(4):1633-1640
Abstract: The axonal outgrowth of cells of Neuro2a, a mouse neuroblastoma cell line, was suppressed on expression of the β-galactoside α1,2-fucosyltransferase (α1,2-FT) gene. We recently cloned two types of rabbit α1,2-FT, RFT-I and RFT-II. RFT-I exhibits comparable kinetic properties and structural homology with human H gene α1,2-FT, and RFT-II shows comparable kinetic parameters with human Se gene α1,2-FT. Neuro2a cells expressing RFT-I (N2A-RFT-I) contained a large amount of fucosyl GM1 instead of GM1 and GD1a, major gangliosides in the parent Neuro2a cells, whereas Neuro2a cells expressing RFT-II (N2A-RFT-II) showed a subtle change in the ganglioside pattern. N2A-RFT-II and parent Neuro2a cells showed axonal outgrowth in serum-free medium on the exogenous addition of GM1, whereas N2A-RFT-I cells exhibited multiple neurite sprouts but not axonal outgrowth. This phenotype was fully recovered by N2A-RFT-I cells on the addition of d - threo -1-phenyl-2-decanoylamino-3-morpholino-1-propanol and α- l -fucosidase to the culture medium, which resulted in pronounced reduction of fucosyl GM1 expression. These results suggested that expression of H-type α1,2-FT, and subsequent incorporation of fucose into glycolipids and glycoproteins, especially the formation of fucosyl GM1, modifies the response of neuronal cells to stimuli that induce axonal extension. 相似文献
19.
A. Belaaouaj C. Moog-Lutz J. Just A. Houzel-Charavel S. D. Shapiro Y. Cayre 《Mammalian genome》1999,10(3):210-212
Proteinase 3 (PR3), is a matrix-degrading serine proteinase expressed in different hematopoietic cell lineages. The PR3 protein
appears to regulate the myeloid differentiation and was found to be the autoantigen associated with Wegener granulomatosis.
We have isolated and characterized the gene for mouse PR3 (mPR3) and determined its chromosomal location. The gene has been localized to Chromosome (Chr) 10. Comparison of mouse PR3 genomic
structure with that of its human counterpart indicates that: 1) the mPR3 gene spans 7 kb organized in 5 exons and 4 introns, 2) the codons of His-Asp-Ser of the catalytic site are conserved and
spread out over different exons, similar to the human gene, and 3) the gene product encodes a pre-proform of the protein.
Knowledge of the structure and chromosomal location of the mPR3 gene may help better the understanding of the temporal and cell-specific expression of mouse PR3.
Received: 14 July 1998 / Accepted: 28 October 1998 相似文献
20.
Takashi Miwa Mayumi Nonaka Noriko Okada Shigeharu Wakana Toshihiko Shiroishi H. Okada 《Immunogenetics》1998,48(6):363-371
Human membrane cofactor protein (MCP, CD46) is widely distributed and is one of the plasma membrane complement inhibitors.
We isolated cDNA clones encoding genetic homologues of human MCP from a rat testis cDNA library. Northern blot analysis indicated
that rat MCP is preferentially expressed in testis, similar to what is found with guinea pig MCP. We identified several different
cDNAs, which were presumably generated by alternative splicing from a single-copy gene. The most prevalent isoform corresponded
to the Ser/Thr/Pro-rich C type of human MCP. Mouse MCP cDNA was cloned by polymerase chain reaction based on the nucleotide
sequence of rat MCP. The deduced amino acid sequence showed 77.8% identity to rat MCP. Mouse MCP was also preferentially expressed
in testis. Unique expression in testis in rat and mouse as well as guinea pig suggests that MCPs in these species not only
act as complement regulatory proteins but may also have more specialized functions in fertilization or reproduction. Genetic
mapping by linkage analysis indicated that the mouse Mcp gene is located on distal chromosome 1, closely linked to the complement receptor 2 (Cr2) gene.
Received: 24 February 1998 / Revised: 11 May 1998 相似文献