Genes and function最新文献

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A novel Xenopus homologue of bone morphogenetic protein-7 (BMP-7) 一种新的爪蟾骨形态发生蛋白-7 (BMP-7)同源物
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00023.x
Shouwen Wang, Marie Krinks, Logan Kleinwaks, Malcolm Moos
{"title":"A novel Xenopus homologue of bone morphogenetic protein-7 (BMP-7)","authors":"Shouwen Wang,&nbsp;Marie Krinks,&nbsp;Logan Kleinwaks,&nbsp;Malcolm Moos","doi":"10.1046/j.1365-4624.1997.00023.x","DOIUrl":"10.1046/j.1365-4624.1997.00023.x","url":null,"abstract":"<p>We identified a<i>Xenopus</i> gene closely related to mammalian bone morphogenetic protein (BMP)-7 (also termed osteogenic protein-1 or OP-1). It resembles the mammalian gene in primary structure and expression pattern much more closely than does a previously described <i>Xenopus</i> homologue, originally termed XBMP-7 [Nishimatsu, Suzuki, Shoda, Murakami and Ueno (1992) Biochem. Biophys. Res. Commun. <b>186</b>, 1487–1495]. The novel gene has therefore been designated XBMP-7 and the gene described earlier has been renamed XBMP-7R (M. Moos and N. Ueno, unpublished work). It has a broad distribution, primarily in the anterior and posterior ventral regions during gastrulation, subsequently becoming prominent at different stages in a wide variety of structures (eyes, neural structures, heart, pronephros, posterior ventral region and other structures), paralleling the distribution of XBMP-4 closely. However, its expression begins later than that of XBMP-4 during gastrulation. Lithium treatment of embryos concentrates the XBMP-7 expression in the expanded eye and heart structures. Ventral overexpression of XBMP-7 produces large protrusions that ultimately develop colouration characteristic of haemoglobin, which is confirmed by markedly expanded expression of α-globin. Dorsal overexpression suppresses dorsal anterior structures. Molecular analysis of animal caps overexpressing XBMP-7 reveals induction of markers associated with ventral and haematopoietic tissue, which is consistent with whole-embryo overexpression results. Globin induction by XBMP-7 can be blocked by a truncated BMP receptor previously shown to interrupt BMP-4 signalling, indicating XBMP-7 also interacts with this receptor. Our data support the concept that XBMP-7 may play a variety of roles during embryogenesis, and suggest a possible role in haematogenesis.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 4","pages":"259-271"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00023.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 33
Selective roles for TATA-binding-protein-associated factors in vivo 体内tata结合蛋白相关因子的选择性作用
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00004.x
Kevin Struhl
{"title":"Selective roles for TATA-binding-protein-associated factors in vivo","authors":"Kevin Struhl","doi":"10.1046/j.1365-4624.1997.00004.x","DOIUrl":"10.1046/j.1365-4624.1997.00004.x","url":null,"abstract":"<p>Transcription factor TFIID, a central component of the eukaryotic RNA polymerase II transcription machinery, is a multiprotein complex containing the TATA-binding protein (TBP) and TBP-associated factors (TAFs). <i>In vitro</i>, TAFs are required for the response to activator proteins, but they are dispensible for basal transcription. However, recent work in yeast cells indicates that TAFs are not generally required for transcriptional activation, but rather have selective effects on gene expression. Molecular mechanisms for these observations are considered.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1","pages":"5-9"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00004.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Gain adaptation and phase dynamics of compensatory eye movements in mice 小鼠代偿性眼动的增益适应和相位动力学
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00018.x
Sebastiaan Koekkoek, Arjan V. Alphen, Johannes V.d. Burg, Frank Grosveld, Niels Galjart, Chris De Zeeuw
{"title":"Gain adaptation and phase dynamics of compensatory eye movements in mice","authors":"Sebastiaan Koekkoek,&nbsp;Arjan V. Alphen,&nbsp;Johannes V.d. Burg,&nbsp;Frank Grosveld,&nbsp;Niels Galjart,&nbsp;Chris De Zeeuw","doi":"10.1046/j.1365-4624.1997.00018.x","DOIUrl":"10.1046/j.1365-4624.1997.00018.x","url":null,"abstract":"<p>The vestibulocerebellum is involved in the control of compensatory eye movements. To investigate its role in the learning and timing of motor behaviour, eye movements in normal and mutant mice were investigated for the first time with the use of search coils. Wild-type mice showed the ability to increase the gain of their vestibulo-ocular reflex by visuo-vestibular training. This adaptation did not occur in <i>lurcher</i> mice, a natural mouse mutant that completely lacks Purkinje cells. During the optokinetic reflex the phase (timing) of the eye movements of <i>lurcher</i>s lagged behind that of wild-type littermates, whereas during the vestibulo-ocular reflex it led that of the wild types. Ablations of different parts of the vestibulocerebellum indicated that the flocculus is necessary for the adaptation and the phase-leading effects of the cerebellum, whereas the nodulus might contribute to its phase-lagging effects. We conclude that Purkinje cells in the vestibulocerebellum are necessary for both learning and timing of compensatory eye movements in mice, and that the flocculus and nodulus may play antagonistic roles in these processes. The present description of the basic principles of cerebellar eye-movement control opens up the possibility to investigate the mechanisms of this motor behaviour at the molecular level in genetically manipulated mutant mice.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 3","pages":"175-190"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00018.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 78
Reprogramming the signalling requirement for AP-1 (activator protein-1) activation during differentiation of precursor CD4+ T-cells into effector Th1 and Th2 cells 前体CD4+ t细胞分化为效应Th1和Th2细胞过程中AP-1(激活蛋白-1)激活的信号需求重编程
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00007.x
Mercedes Rincón, Benoit Dérijard, Chi-Wing Chow, Roger Davis, Richard Flavell
{"title":"Reprogramming the signalling requirement for AP-1 (activator protein-1) activation during differentiation of precursor CD4+ T-cells into effector Th1 and Th2 cells","authors":"Mercedes Rincón,&nbsp;Benoit Dérijard,&nbsp;Chi-Wing Chow,&nbsp;Roger Davis,&nbsp;Richard Flavell","doi":"10.1046/j.1365-4624.1997.00007.x","DOIUrl":"10.1046/j.1365-4624.1997.00007.x","url":null,"abstract":"<p>Upon antigenic stimulation, precursor CD4<sup>+</sup> helper T-cells differentiate into two subsets of effector cells, Th1 and Th2. These two subpopulations are defined by the pattern of cytokine expression that distinguishes these differentiated cells from their precursors. We have used reporter transgenic mice here to show that, during differentiation of precursor T-cells into effector Th1 or Th2 cells, high levels of preformed activator protein (AP)-1 complexes are accumulated. However, upon stimulation, the preformed AP-1 complexes in effector Th2 cells, but not in Th1 cells, are able to induce high levels of AP-1 transcriptional activity. Furthermore, in contrast to precursor T-cells, the induction of AP-1 transcriptional activity is independent of calcium and co-stimulatory signals in effector Th2 cells. This AP-1 transcriptional activity appears to correlate with the presence of JunB complexes, which accumulate differentially in effector Th2 cells, but not in precursor CD4<sup>+</sup> T-cells or effector Th1 cells. Unlike precursor cells, the activation of AP-1 does not appear to be mediated by c-Jun N-terminal kinase (JNK) in effector Th2 cells. These results indicate that during differentiation of T-cells, and probably other cell types, the signal requirements for the AP-1 transcription machinery are reprogrammed to enable the differentiated cells to perform their specialized functions.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1","pages":"51-68"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00007.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 127
one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube 单眼针尖是斑马鱼神经管腹中线发育所必需的
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00010.x
Uwe Strähle, Suresh Jesuthasan, Patrick Blader, Pilar Garcia-Villalba,  Kohei Hatta, Philip W. Ingham
{"title":"one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube","authors":"Uwe Strähle,&nbsp;Suresh Jesuthasan,&nbsp;Patrick Blader,&nbsp;Pilar Garcia-Villalba,&nbsp; Kohei Hatta,&nbsp;Philip W. Ingham","doi":"10.1046/j.1365-4624.1997.00010.x","DOIUrl":"10.1046/j.1365-4624.1997.00010.x","url":null,"abstract":"<p>Axial midline structures play a central role as signalling centres during the development of the vertebrate embryo. We have isolated mutant alleles of a new locus, <i>one-eyed pinhead </i>(<i>oep</i>), in the zebrafish that are characterized by cyclopia and impaired development of the floor plate. <i>oep</i> mutants fail to establish expression of <i>axial</i> (zebrafish <i>HNF3β</i>) and <i>sonic hedgehog</i> in the midline of the neural plate but form a notochord that expresses both genes. In the spinal cord of the 1-day-old embryo, mutation of <i>oep</i> impairs floor-plate but not motor-neuron development. Floor-plate development is absolutely dependent on <i>oep</i> only at early stages, since partial recovery of the floor plate can be detected at 48 h in the spinal cord, suggesting compensatory pathways. Ectopic expression of <i>sonic hedgehog</i> and a dominant-negative protein kinase A regulatory subunit induces expression of floor-plate marker genes in the <i>oep</i> mutant neural tube in a manner indistinguishable from wild-type embryos. Our data suggest that the <i>oep</i> mutation does not impair Sonic hedgehog signalling and thus implicate a second process that acts synergistically with Sonic hedgehog signalling in the specification of the midline of the neuroectoderm and that can partially be compensated for during later development.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 2","pages":"131-148"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00010.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20598004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 99
HIV integrase: a target for drug discovery HIV整合酶:药物发现的靶标
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00026.x
Ramon Puras Lutzke, Ronald Plasterk
{"title":"HIV integrase: a target for drug discovery","authors":"Ramon Puras Lutzke,&nbsp;Ronald Plasterk","doi":"10.1046/j.1365-4624.1997.00026.x","DOIUrl":"10.1046/j.1365-4624.1997.00026.x","url":null,"abstract":"<p>Current antiviral strategies against HIV rely on structure–function analysis of HIV reverse transcriptase (RT) and protease (PR). The third viral <i>pol</i> gene product, HIV integrase (IN), is also a good target for drug discovery, since IN is essential for retroviral replication and, moreover, it has no obvious functional analogue in the host. IN forms a ternary complex with metal ions and DNA and has a mechanism of catalysis common with other polynucleotidyl transferases. Although there is no structural information for full-length IN available, structures of all three functional IN domains have been determined by X-ray crystallography and NMR spectroscopy. The N-terminal domain has a novel zinc-binding fold, the catalytic domain shares a common structural motif with other polynucleotidyl transferases, and the C-terminal DNA-binding domain has a Src-homology-3-like fold. This structural information provides the basis for drug development. In turn, increasing numbers of IN inhibitors identified so far may serve structure–function analysis of IN. The final goal is the development of new classes of anti-HIV drugs, which can be added to the repertoire of anti-RT and anti-PR drugs.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 5","pages":"289-307"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00026.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26610202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Functional analysis of a 38 kilobase region on chromosome XVI inSaccharomyces cerevisiae 酿酒酵母XVI染色体38千碱基区功能分析
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00025.x
Sophia Ushinsky, Howard Bussey, Alia Ahmed, Ying Wang, James Friesen, Reginald Storms
{"title":"Functional analysis of a 38 kilobase region on chromosome XVI inSaccharomyces cerevisiae","authors":"Sophia Ushinsky,&nbsp;Howard Bussey,&nbsp;Alia Ahmed,&nbsp;Ying Wang,&nbsp;James Friesen,&nbsp;Reginald Storms","doi":"10.1046/j.1365-4624.1997.00025.x","DOIUrl":"10.1046/j.1365-4624.1997.00025.x","url":null,"abstract":"<p>In this report we assess the functional importance of 16 open reading frames (ORFs) contained within a 38 780 base-pair region immediately adjacent to the centromere on the right arm of chromosome XVI in <i>Saccharomyces cerevisiae.</i> This analysis involved replacing one copy of each ORF in a diploid strain with a cassette encoding the green fluorescent protein from the jellyfish <i>Aequorea victoria</i> and <i>HIS3.</i> Each replacement cassette was generated by PCR using oligonucleotide pairs with 45-base extensions complementary to sequences immediately upstream and downstream of the target gene’s coding region. After replacement of the targeted genes, each gene-replacement strain was subjected to a series of genetic and phenotypic tests to assess the functional importance of the deleted gene. This analysis showed that two ORFs were essential, one for spores to germinate and another for vegetative growth. A third gene encoded a copper-fist-like transcription factor that was required for proper bud-site selection. One of the 16 ORFs was duplicated, a situation not observed in the strain used to sequence the yeast genome (S288C). RNA analysis showed 11 of the 16 ORFs in this region expressed steady-state poly(A<sup>+</sup>) RNA levels that were greater than or equal to 2% of the level expressed from the yeast actin gene, <i>ACT1.</i></p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 4","pages":"273-284"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00025.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Recombination and joining: different means to the same ends 重组和连接:不同的手段达到相同的目的
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00016.x
Roland Kanaar, Jan Hoeijmakers
{"title":"Recombination and joining: different means to the same ends","authors":"Roland Kanaar,&nbsp;Jan Hoeijmakers","doi":"10.1046/j.1365-4624.1997.00016.x","DOIUrl":"10.1046/j.1365-4624.1997.00016.x","url":null,"abstract":"<p>DNA double-strand breaks are very genotoxic lesions that can result in chromosome aberrations. The current view is that DNA double-strand breaks are repaired most efficiently through homologous recombination in yeast and simple end-joining in mammalian cells. However, recent experiments reveal that both repair pathways are conserved from yeast to mammals, including humans. The challenge ahead is to put the different pieces of the jigsaw together into coherent mechanisms for both pathways and to determine their relative contributions to ionizing-radiation resistance and to the prevention of genetic instability and carcinogenesis.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 3","pages":"165-174"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00016.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 60
Genomic regions regulating imprinting and insulin-like growth factor-II promoter 3 activity in transgenics: novel enhancer and silencer elements 转基因基因中调控印迹和胰岛素样生长因子- ii启动子3活性的基因组区域:新的增强子和沉默子元件
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00001.x
Andrew Ward, Rosie Fisher, Lynne Richardson, Jo-Anna Pooler, Sarah Squire, Phil Bates, Rimma Shaposhnikov, Neil Hayward, Milo Thurston, Chris Graham
{"title":"Genomic regions regulating imprinting and insulin-like growth factor-II promoter 3 activity in transgenics: novel enhancer and silencer elements","authors":"Andrew Ward,&nbsp;Rosie Fisher,&nbsp;Lynne Richardson,&nbsp;Jo-Anna Pooler,&nbsp;Sarah Squire,&nbsp;Phil Bates,&nbsp;Rimma Shaposhnikov,&nbsp;Neil Hayward,&nbsp;Milo Thurston,&nbsp;Chris Graham","doi":"10.1046/j.1365-4624.1997.00001.x","DOIUrl":"10.1046/j.1365-4624.1997.00001.x","url":null,"abstract":"<p>Transgenic lines (89) were made with constructs containing eight different combinations of candidate regulatory elements from the insulin-like growth factor-II (<i>Igf2</i>)–<i>H19</i> region of mouse chromosome 7. In all constructs, promoter 3 of <i>Igf2</i> was attached to a firefly luciferase reporter gene. Promoter 3 was the common element that imposed a decrease in reporter activity similar to that of endogenous <i>Igf2</i> after birth. The specific activity of the reporter was measured on the day of birth in the liver and the brain, after each transgene had been transmitted by either the father or the mother. This procedure demonstrated that the quantity and organ distribution of expression from this promoter can be regulated by each element. The following new information was obtained. (a) The 5′ differentially methylated region of <i>Igf2</i> inhibits promoter 3 in the liver. (b) The conserved DNase I-hypersensitive Middle region between <i>Igf2</i> and <i>H19</i> is an enhancer of promoter 3 in the brain. (c) The <i>H19</i> promoter inhibits <i>Igf2</i> promoter 3 in the brain. The results confirmed that the <i>H19</i> enhancer is a strong enhancer of promoter 3 in the liver. A new finding was that one genomic region regularly imposed imprinted gene expression. This was the <i>H19</i> enhancer, and this region was sufficient to give higher expression on maternal transmission in the majority of transgenic lines. The full data are reported in Supplementary Publication SUP 50180 (8 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1997) <b>21</b>, 8–10.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1","pages":"25-36"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00001.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 20
Mutation analysis of the mouse myosin VIIA deafness gene 小鼠肌球蛋白via耳聋基因突变分析
Genes and function Pub Date : 2008-06-28 DOI: 10.1046/j.1365-4624.1997.00020.x
Philomena Mburu, Xue Zhong Liu, James Walsh, Dennis Saw, M. Cope, Fernando Gibson, John Kendrick-Jones, Karen Steel, Steve Brown
{"title":"Mutation analysis of the mouse myosin VIIA deafness gene","authors":"Philomena Mburu,&nbsp;Xue Zhong Liu,&nbsp;James Walsh,&nbsp;Dennis Saw,&nbsp;M. Cope,&nbsp;Fernando Gibson,&nbsp;John Kendrick-Jones,&nbsp;Karen Steel,&nbsp;Steve Brown","doi":"10.1046/j.1365-4624.1997.00020.x","DOIUrl":"10.1046/j.1365-4624.1997.00020.x","url":null,"abstract":"<p>The shaker-1 (<i>Myo7a</i>) mouse deafness locus is encoded by an unconventional myosin gene: myosin VIIA [Gibson, Walsh, Mburu, Varela, Brown, Antonio, Biesel, Steel and Brown (1995) Nature (London) <b>374</b>, 62–64]. The myosin VIIA gene is expressed in hair cells in the cochlea, where it is thought to function in the development of the critical neuroepithelium where auditory transduction takes place. In order to understand better the function of myosin VIIA, we have determined the complete sequence of the mouse myosin VIIA cDNA and employed the wild-type sequence for mutational analysis of a number of shaker-1 alleles. Analysis of the mouse myosin VIIA tail sequence demonstrates a large internal repeat with regions of similarity to myosins IV, X and XII as well as members of the band 4.1 family. In addition, the myosin VIIA repeats are similar along their entire length to a tail domain from a plant kinesin. The mouse myosin VIIA tail also contains a putative Src homology 3 (SH3) domain. Along with three previously reported shaker-1 mutations, mutations for seven shaker-1 alleles in total have now been identified. The mutational changes have been analysed in terms of their predicted effect on both myosin motor head and tail domain function and the predictions related to the known phenotypes of the shaker-1 alleles. Five of the mutations lie in the motor head, and analysis of their likely effect on myosin head structure correlates well with the known severity of the shaker-1 alleles. Of the two mutations in the tail, one is a missense mutation within the kinesin and myosin IV, X and XII homology domains that substitutes a conserved amino acid and leads to a severe deafness phenotype. This and other data suggest that myosin VIIA may have properties of a myosin-motor–kinesin-tail hybrid and be involved in membrane turnover within the actin-rich environment of the apical hair cell surface.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 3","pages":"191-203"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00020.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 113
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