共查询到20条相似文献，搜索用时 31 毫秒
1.
Goyenvalle A Vulin A Fougerousse F Leturcq F Kaplan JC Garcia L Danos O 《Science (New York, N.Y.)》2004,306(5702):1796-1799
Most mutations in the dystrophin gene create a frameshift or a stop in the mRNA and are associated with severe Duchenne muscular dystrophy. Exon skipping that naturally occurs at low frequency sometimes eliminates the mutation and leads to the production of a rescued protein. We have achieved persistent exon skipping that removes the mutated exon on the dystrophin messenger mRNA of the mdx mouse, by a single administration of an AAV vector expressing antisense sequences linked to a modified U7 small nuclear RNA. We report the sustained production of functional dystrophin at physiological levels in entire groups of muscles and the correction of the muscular dystrophy. 相似文献
2.
Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin 总被引：25，自引：0，他引：25
Elevated free Ca2+ concentrations found in adult dystrophic muscle fibers result in enhanced protein degradation. Since the difference in concentrations may reflect differences in entry, Ca2+ leak channels in cultures of normal and Duchenne human myotubes, and normal and mdx murine myotubes, have been identified and characterized. The open probability of leak channels is markedly increased in dystrophic myotubes. Other channel properties, such as mean open times, single channel conductance, ion selectivity, and behavior in the presence of pharmacological agents, were similar among myotube types. Compared to the Ca2+ concentrations in normal human and normal mouse myotubes, intracellular resting free Ca2+ concentrations ([Ca2+]i) in myotubes of Duchenne and mdx origin were significantly higher at a time when dystrophin is first expressed in normal tissue. Taken together, these findings suggest that the increased open probability of Ca2+ leak channels contributes to the elevated free intracellular Ca2+ concentration in Duchenne human and mdx mouse myotubes. 相似文献
3.
Fibroblast growth factor in the extracellular matrix of dystrophic (mdx) mouse muscle 总被引：14，自引：0，他引：14
Polyclonal antibody F547 reacts with a bovine basic fibroblast growth factor (bFGF) and a human recombinant bFGF, but not with bovine acidic fibroblast growth factor. This antibody localized bFGF in the extracellular matrix of mouse skeletal muscle, primarily in the fiber endomysium, which includes the heparin-containing basal lamina. In mdx mouse muscle, which displays persistent regeneration, FGF levels in the extracellular matrix are higher than those in controls. Overabundance of matrix FGF in mdx muscles may be related to an increase in both satellite cell and regenerative activity in the dystrophic muscle and may help explain the benign phenotype of mdx animals compared with the genetically identical human Duchenne muscular dystrophy. 相似文献
4.
The molecular basis of the sparse fur mouse mutation 总被引：30，自引：0，他引：30
The ornithine transcarbamylase-deficient sparse fur mouse is an excellent model to study the most common human urea cycle disorder. The mutation has been well characterized by both biochemical and enzymological methods, but its exact nature has not been revealed. A single base substitution in the complementary DNA for ornithine transcarbamylase from the sparse fur mouse has been identified by means of a combination of two recently described techniques for rapid mutational analysis. This strategy is simpler than conventional complementary DNA library construction, screening, and sequencing, which has often been used to find a new mutation. The ornithine transcarbamylase gene in the sparse fur mouse contains a C to A transversion that alters a histidine residue to an asparagine residue at amino acid 117. 相似文献
5.
J S Chamberlain J A Pearlman D M Muzny R A Gibbs J E Ranier C T Caskey A A Reeves 《Science (New York, N.Y.)》1988,239(4846):1416-1418
Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations. 相似文献
6.
A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse 总被引：81，自引：0，他引：81
In a pedigree derived from a mouse treated with the mutagen ethylnitrosourea, a mutation has been identified that predisposes to spontaneous intestinal cancer. The mutant gene was found to be dominantly expressed and fully penetrant. Affected mice developed multiple adenomas throughout the entire intestinal tract at an early age. 相似文献
7.
Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance 总被引：26，自引：0，他引：26
T Kadowaki C L Bevins A Cama K Ojamaa B Marcus-Samuels H Kadowaki L Beitz C McKeon S I Taylor 《Science (New York, N.Y.)》1988,240(4853):787-790
Insulin receptor complementary DNA has been cloned from an insulin-resistant patient with leprechaunism whose receptors exhibited multiple abnormalities in insulin binding. The patient is a compound heterozygote, having inherited two different mutant alleles of the insulin receptor gene. One allele contains a missense mutation encoding the substitution of glutamic acid for lysine at position 460 in the alpha subunit of the receptor. The second allele has a nonsense mutation causing premature chain termination after amino acid 671 in the alpha subunit, thereby deleting both the transmembrane and tyrosine kinase domains of the receptor. Interestingly, the father is heterozygous for this nonsense mutation and exhibits a moderate degree of insulin resistance. This raises the possibility that mutations in the insulin receptor gene may account for the insulin resistance in some patients with non-insulin-dependent diabetes mellitus. 相似文献
8.
Human immunoglobulin D: genomic sequence of the delta heavy chain 总被引：11，自引：0，他引：11
M B White A L Shen C J Word P W Tucker F R Blattner 《Science (New York, N.Y.)》1985,228(4700):733-737
The DNA coding for the human immunoglobulin D(IgD) heavy chain (delta, delta) has been sequenced including the membrane and secreted termini. Human delta, like that of the mouse, has a separate exon for the carboxyl terminus of the secreted form. This feature of human and mouse IgD distinguishes it from all other immunoglobulins regardless of species or class. The human gene is different from that of the mouse; it has three, rather than two, constant region domains; and its lengthy hinge is encoded by two exons rather than one. Except for the third constant region, the human and mouse genes are only distantly related. 相似文献
9.
J genes for heavy chain immunoglobulins of mouse 总被引：15，自引：0，他引：15
A 15,8-kilobase pair fragment of BALB/c mouse liver DNA, cloned in the Charon 4A lambda phage vector system, was shown to contain the mu heavy chain constant region (CHmu) gene for the mouse immunoglobulin M. In addition, this fragment of DNA contains at least two J genes, used to code for the carboxyl terminal portion of heavy chain variable regions. These genes are located in genomic DNA about eight kilobase pairs to the 5' side of the CHmu gene. The complete nucleotide sequence of a 1120-base pair stretch of DNA that includes the two J genes has been determined. 相似文献
10.
Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse 总被引：1，自引：0，他引：1
Serizawa S Miyamichi K Nakatani H Suzuki M Saito M Yoshihara Y Sakano H 《Science (New York, N.Y.)》2003,302(5653):2088-2094
In the mouse olfactory system, each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) gene in a monoallelic and mutually exclusive manner. Such expression forms the genetic basis for OR-instructed axonal projection of OSNs to the olfactory bulb of the brain during development. Here, we identify an upstream cis-acting DNA region that activates the OR gene cluster in mouse and allows the expression of only one OR gene within the cluster. Deletion of the coding region of the expressed OR gene or a naturally occurring frame-shift mutation allows a second OR gene to be expressed. We propose that stochastic activation of only one OR gene within the cluster and negative feedback regulation by that OR gene product are necessary to ensure the one receptor-one neuron rule. 相似文献
11.
植物病原真菌对几类重要单位点杀菌剂的抗药性分子机制 总被引：18，自引：1，他引：17
单位点杀菌剂是植物病害管理的重要组成部分,随着单位点杀菌剂的大量、广泛使用,抗性问题也随之产生。目前为止,有植物病原菌对各大类单位点杀菌剂均具抗性的报道。本文作者主要阐述了生产中常用的5类单位点杀菌剂,包括苯并咪唑类杀菌剂（MBCs）、二甲酰亚胺类杀菌剂（DCFs）、14α-脱甲基酶抑制剂（DMIs）、QoIs和琥珀酸脱氢酶抑制剂（SDHIs）的作用机理及抗性分子机制的研究进展,并进一步论述了抗药性产生的机理及抗性治理原则。MBCs作用于β-微管蛋白,抗性主要与靶标蛋白基因的点突变有关,突变造成的氨基酸变化多集中于第50、167、198、200和240等5个位置,主要突变位点为第198位,同一菌株通常只发生一个氨基酸变异,不同位点的点突变甚至同一位点的不同氨基酸替代均会引起抗性水平的差异;DCFs的作用靶标尚不清楚,病原真菌对其抗性可能与双元组氨酸激酶OS基因的点突变有关;DMIs通过抑制14α-脱甲基酶最终影响麦角甾醇的合成,抗性主要与Cyp51的点突变或过量表达或运输体的过量表达相关,Cyp51点突变是抗DMI的主要机制,同一突变对不同的三唑类杀菌剂敏感性表现不尽相同,不同位置的点突变在同一病原菌中对不同三唑类杀菌剂的敏感性影响也不同。点突变数量在不同的真菌中表现不同,有单个发生,也有多个同时发生,且对抗药性具有积累效应;QoIs作用于电子传递链的复合物III,抗性主要与Cytb的点突变有关,与抗性相关的点突变主要发生在Cytb的120-155和255-280两个编码区,其中G143A和F129L为最主要的点突变;SDHIs作用于电子传递链的复合物II,抗性主要与SdhB、SdhC或SdhD的点突变有关,大部分病原真菌对SDHIs的抗性与SdhB点突变有关,SdhB点突变发生位置比较单一,在多种病原菌中突变均发生在相同的组氨酸上即H272, 而SdhC和SdhD突变位点比较多。 相似文献
12.
G P Smith 《Science (New York, N.Y.)》1973,181(103):941-943
The kappa chain from the immunoglobulin of myeloma tumor MPC 11 has 12 extra residues at its amino terminus, the first six of which are identical to the residues at positions 1 to 6 of typical mouse kappa chains and at positionss 13 to 18 of MPC 11 itself. Two of the peptide bonds within this extra 12-residue segment are cleaved under very mild conditions. 相似文献
13.
Reshaping human antibodies: grafting an antilysozyme activity 总被引：24，自引：0，他引：24
The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the "humanizing" of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism. 相似文献
14.
Identification of a chromosome 18q gene that is altered in colorectal cancers 总被引：141，自引：0，他引：141
E R Fearon K R Cho J M Nigro S E Kern J W Simons J M Ruppert S R Hamilton A C Preisinger G Thomas K W Kinzler 《Science (New York, N.Y.)》1990,247(4938):49-56
Allelic deletions involving chromosome 18q occur in more than 70 percent of colorectal cancers. Such deletions are thought to signal the existence of a tumor suppressor gene in the affected region, but until now a candidate suppressor gene on this chromosomal arm had not been identified. A contiguous stretch of DNA comprising 370 kilobase pairs (kb) has now been cloned from a region of chromosome 18q suspected to reside near this gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an "exon-connection" strategy based on the polymerase chain reaction. Expressed exons were used as probes for cDNA screening to obtain clones that encoded a portion of a gene termed DCC; this cDNA was encoded by at least eight exons within the 370-kb genomic region. The predicted amino acid sequence of the cDNA specified a protein with sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5' end of the gene, a point mutation within one of the introns, and ten examples of DNA insertions within a 0.17-kb fragment immediately downstream of one of the exons. The DCC gene may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth. 相似文献
15.
16.
Discrete visual defects in pearl mutant mice 总被引：3，自引：0，他引：3
The mutant mouse pearl, characterized by its hypopigmentation, has a specific functional defect in a sensory system--the retina. The intact pearl mouse has reduced sensitivity in the dark-adapted condition. Normal sensitivity is restored by isolation and superfusion of the retina with bicarbonate-buffered Ringer solution, suggesting that the retinal expression of the pearl mutation depends on a diffusible substance. The pearl phenotype is described as a possible model for human congenital stationary night blindness. 相似文献
17.
Somatic mutation in genes for the variable portion of the immunoglobulin heavy chain 总被引：11，自引：0，他引：11
J Sims T H Rabbitts P Estess C Slaughter P W Tucker J D Capra 《Science (New York, N.Y.)》1982,216(4543):309-311
The size of the gene pool potentially encoding antibodies to p-azophenyl arsonate has been examined. A heavy chain-specific full-length complementary DNA clone has been constructed with the use of messenger RNA from a hybridoma that produces antibodies to the arsonate hapten and bears nearly a full complement of the determinants comprising the cross-reactive idiotype (CRI). The sequences of both the complementary DNA clone and the corresponding immunoglobulin heavy chain have been independently determined. A probe for the variable region gene was prepared from the original heavy chain complementary DNA clone and used to analyze, by Southern filter hybridization, genomic DNA from both A/J (CRI positive) and BALB/c (CRI negative) mice. Approximately 20 to 25 restriction fragments containing "germline" variable region gene segments were detected in both strains, and many are shared by both, Since 35 CRI-positive heavy chains have been partially sequenced thus far and 31 are different, the results of the hybridization analysis suggest that somatic mutation events involving the variable region gene segments of the heavy chain play a role in the origin of the amino acid sequence diversity seen in this system. 相似文献
18.
Montarras D Morgan J Collins C Relaix F Zaffran S Cumano A Partridge T Buckingham M 《Science (New York, N.Y.)》2005,309(5743):2064-2067
Muscle satellite cells contribute to muscle regeneration. We have used a Pax3(GFP/+) mouse line to directly isolate (Pax3)(green fluorescent protein)-expressing muscle satellite cells, by flow cytometry from adult skeletal muscles, as a homogeneous population of small, nongranular, Pax7+, CD34+, CD45-, Sca1- cells. The flow cytometry parameters thus established enabled us to isolate satellite cells from wild-type muscles. Such cells, grafted into muscles of mdx nu/nu mice, contributed both to fiber repair and to the muscle satellite cell compartment. Expansion of these cells in culture before engraftment reduced their regenerative capacity. 相似文献
19.
Mutation to herbicide resistance maps within the psbA gene of Anacystis nidulans R2 总被引：11，自引：0，他引：11
A psbA gene encoding the target of photosystem II herbicide inhibition, the 32,000-dalton thylakoid membrane protein, has been cloned from a mutant of Anacystis nidulans R2, which is resistant to 3-(3,4-dichlorophenyl)-1,1-dimethylurea-(diuron). A cloned DNA fragment from within the coding region of this gene transforms wild-type cells to herbicide resistance, proving that mutation within psbA is responsible for that phenotype. The mutation consists of a single nucleotide change that replaces serine at position 264 of the wild-type protein with alanine in that of the diuron-resistant mutant. 相似文献
20.
CRISPR编辑系统结合高通量测序,可实现高效评估基因编辑效率和准确度,并在遗传学、生物学、医学等多个领域得到广泛应用。然而,高通量测序数据缺乏一个一键流程化界面工具来实现突变效率和准确度的评估。为此,开发了一个基于Python的可视化工具——作物基因编辑效果可视化鉴定软件。该软件可对高通量基因编辑数据进行批量计算,可一键实现数据的预处理(拆分和合并)、突变类型和效率的检测和可视化图表输出。该软件提供了界面化程序,用户只需鼠标点击即可实现数据的导入和结果的输出。分析结果以多种格式输出,图像支持缩放和颜色更改,方便后期结果整理和撰写论文。此外,该软件安装使用简单,并支持多操作系统(Windows、Linux和MacOS)使用。目前该软件的使用手册和程序包已上传到开放软件平台,方便下载和使用。 相似文献