共查询到20条相似文献,搜索用时 15 毫秒
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Aline Primot Ariane Mogha Sébastien Corre Karen Roberts Julien Debbache Henri Adamski Brigitte Dreno Amir Khammari Thierry Lesimple Agnes Mereau Colin R Goding Marie-Dominique Galibert 《Pigment cell & melanoma research》2010,23(1):93-102
The master regulator of the melanocyte lineage Mitf is intimately involved in development as well as melanoma, controlling cell survival, differentiation, proliferation and metastasis/migration. Consistent with its central role, Mitf expression and Mitf post-translational modifications are tightly regulated. An additional potential level of regulation is afforded by differential splicing of Mitf exon-6 leading to the generation of two isoforms that differ by the presence of six amino-acids in the Mitf (+) isoform and which have differential effects on cell cycle progression. However, whether the ratio of the two isoforms is regulated and whether their expression correlates with melanoma progression is not known. Here, we show that the differential expression of the Mitf 6a/b isoforms is dependent on the MAPKinase signalling, being linked to the activation of MEK1-ERK2, but not to N-RAS/B-RAF mutation status. In addition, quantification of Mitf 6a/b splicing forms in 86 melanoma samples revealed substantially increased levels of the Mitf (−) form in a subset of metastatic melanomas. The results suggest that differential expression of the Mitf 6a/b isoforms may represent an additional mechanism for regulating Mitf function and melanoma biology. 相似文献
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T. Kozlova Lucia Perezgasga Enrique Reynaud Mario Zurita 《Development genes and evolution》1997,207(4):253-263
The hsp60 (heat-shock protein 60) gene family of molecular chaperones has been a subject of study in numerous systems due to its important role in the correct
folding of non-native proteins in development as well as after heat-shock treatment. Here we present the characterization
of the first Drosophila hsp60 homologue. Drosophila HSP60 is most closely related (72% identity across the entire protein sequence) to the mouse mitochondrial HSP60. Western
blot experiments indicate that Drosophila HSP60 is enriched in the mitochondrial fraction. The distribution of HSP60 protein is dynamic during fly embryogenesis, suggesting
that various cell types might have different HSP60 requirements. The molecular analysis of a P-element-induced mutation that
affects the l(1)10Ac locus shows that the transposon is inserted in a 3-kb intron present in the hsp60 gene. By genetic rescue experiments we prove that Drosophila HSP60 is encoded by the essential locus l(1)10Ac opening the possibility for detailed genetic analysis of HSP60 functions in the fly.
Received: 24 March 1997 / Accepted: 16 June 1997 相似文献
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Christina Ni Deming Zhang Lisa A. Beyer Karin E. Halsey Hideto Fukui Yehoash Raphael David F. Dolan Thomas J. Hornyak 《Pigment cell & melanoma research》2013,26(1):78-87
The human deafness‐pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia‐White (MitfMi‐wh/+) mice were studied and hearing function of these mice characterized. MitfMi‐wh/+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. MitfMi‐wh/+ embryos have fewer melanoblasts during embryonic development than their wild‐type littermates. Although cochlear melanocytes are present at birth, they disappear from the MitfMi‐wh/+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness‐pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. 相似文献
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In order for the retina to function properly, photoreceptor cell outer segments must be in contact with the adjacent retinal pigmented epithelium (RPE). A mouse model homozygous for the vitiligo mutation of the microphthalmia (Mitf) gene manifests disruption of the outer segment/RPE interdigitation and demonstrates progressive loss of the photoreceptor cells. The mouse nevertheless has near normal levels of rhodopsin for many weeks and it is not known whether there is an in vivo loss of adhesion or whether the disruption is visible following tissue processing for histology. To assess this, a mechanical separation experiment was performed in which neural retinas were peeled free from the RPE and examined for the amount of pigment adherent to them. The peeling experiment indicated that control neural retinas retained significant amounts of adherent pigment at all ages examined. Neural retinas of mutant mice at age 2 weeks demonstrated adherent pigment, but older animals retained minimal pigment. Scanning electron microscopy indicated that the RPE cells of control mice were markedly damaged upon peeling and displayed different planes of cleavage, whereas those of mutants showed minimal cellular damage upon peeling, suggestive of decreased adhesion. A recombination experiment revealed that the mutant RPE/eyecup could reappose mutant and control retinas under in vitro conditions, suggesting that RPE fluid transport abilities were intact. The data provide the first direct experimental evidence that the Mitfvit mutant mouse has a naturally occurring retinal detachment and hence support its value as a model for studies of retina/RPE adhesion. 相似文献
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The albino mouse was already known in ancient times and was apparently selectively bred in Egypt, China, and Japan. Thus, it is not surprising that the c or albino locus (now the Tyr locus) was among the first used to demonstrate Mendelian inheritance in mammals at the dawn of the past century. This locus is now known to encode tyrosinase, the rate-limiting enzyme in the production of melanin pigment, and the molecular basis of the albino (Tyr
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) mutation is known. Here we describe the congenic series of Tyr-locus alleles, from wild type to null (albino). We compare eye and skin pigmentation phenotypes and the genetic lesions that cause each. We suggest that this panel of congenic mutants contains rich, untapped resources for the study of many questions of basic cell biological interest. 相似文献
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H. Yu X. Wang H. Chen M. Wang M. Zhao X.Y. Lan C.Z. Lei K.Y. Wang X.S. Lai X.L. Wang 《Small Ruminant Research》2008,80(1-3):111-115
The keratins and keratin-associated proteins (KAPs) are a large heterogeneous group of proteins that make up about 90% of the cashmere fiber. Keratin-associated proteins 9.2 gene (KAP9.2) is one of the ultra high sulfur KAPs, which might play an important role in the bundling of intermediate filaments. In this study, the deletion/insertion mutation of KAP9.2 gene in 997 cashmere goat samples was firstly detected, at the same time, parts of these samples were sequenced. The results showed that two alleles were detected at this KAP9.2P1 locus, named allele W and D. The frequencies of the KAP9.2-W allele in Inner Mongolia White cashmere (n = 785) and Shaanbei White cashmere goat breeds (n = 212) were 0.878 and 0.790, respectively. The χ2-test showed that the genotype distributions in these two cashmere goat breeds were not in agreement with Hardy–Weinberg equilibrium. According to the classification of polymorphism information content (PIC), Shaanbei White cashmere goat was more polymorphic at this locus. Moreover a 30 bp-deletion mutation was described at KAP9.2P2 locus for the first time and no deletion/insertion was described at KAP9.2P1 locus. The results possibly revealed that the size polymorphism existed in the two Chinese cashmere goat and the 30 bp-deletion mutation was possibly caused by variations in the number of the decapeptide repeat structures. 相似文献
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Ian W. Dawes Deirdre A. Mackinnon Dianne E. Ball Ian D. Hardie Diana M. Sweet 《Molecular & general genetics : MGG》1977,152(1):53-57
Summary
N-methyl-N-nitro-N-nitrosoguanidine (NG) induces certain classes of multiple mutations in yeast at high frequency. By selecting for mutation at one locus (his4 or leu1) one frequently obtains double mutants where another mutation to temperature sensitivity has also been induced. This multiple mutagenesis exhibits a considerable specificity: for mutation at one particular locus there is a high chance that another mutation will be found in the same cell at one of a restricted number of other loci. For any given locus (e.g. his4) there is a spectrum of sites at which temperature-sensitivity mutations are coinduced. This spectrum differs for different loci, such that the spectrum of sites co-mutating with leul differs completely from that for sites co-mutating with his4. This NG-induced co-mutation is interpreted in terms of NG acting to enhance mutagenesis at sites of simultaneous DNA replication within the cell. The results so obtained indicate a very strict control over the order and timing of gene replication in Saccharomyces cerevisiae, and it is suggested that it is now possible to use NG double mutagenesis to try and locate origins of replication in yeast. 相似文献
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Summary The nnu mutant of Gibberella zeae (= Fusarium graminearum) is unable to catabolize many of the nitrogen sources utilized by its wild-type parent, and may have suffered a mutation in the major nitrogen regulatory locus. Transformation of this mutant with the major nitrogen regulatory gene from Neurospora crassa, nit-2, restored the wild-type phenotype, thus confirming that the nnu mutation is in the major nitrogen regulatory locus of G. zeae. Our results are consistent with the premise of conservation of the structure of regulatory factors and suggest the possibility that functional DNA homologues of this regulatory element occur across a broad range of ascomycetous fungi. 相似文献
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Although alternative life‐history strategies exist within many populations, very little is known about their genetic basis and mechanistic insight into these traits could greatly advance the understanding of eco‐evolutionary dynamics. Many species of butterfly within the genus Colias exhibit a sex‐limited wing colour polymorphism, called Alba, which is correlated with an alternative life‐history strategy. Here, we have taken the first steps in localizing the region carrying Alba in Colias croceus, a species with no genomic resources, by generating whole genome sequence of a single Alba mother and two sequencing pools, one for her Alba and another for her orange, offspring. These data were used in a bulk‐segregant analysis wherein SNPs fulfilling the Mendelian inheritance expectations of Alba were identified. Then, using the conserved synteny in Lepidoptera, the Alba locus was assigned to chromosome 15 in Bombyx mori. We then identified candidate regions within the chromosome by investigating the distribution of Alba SNPs along the chromosome and the difference in nucleotide diversity in exons between the two pools. A region spanning ~ 5.7 Mbp at the 5′ end of the chromosome was identified as likely to contain the Alba locus. These insights set the stage for more detailed genomic scans and mapping of the Alba phenotype, and demonstrate an efficient use of genomic resources in a novel species. 相似文献
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《Bioscience, biotechnology, and biochemistry》2013,77(3):540-545
An acidic-phospholipid deficiency caused by the pgsA3 allele that encodes a defective phosphatidylglycerophosphate synthase in Escherichia coli is lethal. The only known mutations that suppress this lethality fully have been related to the major outer-membrane lipoprotein. We isolated a Bacillus subtilis chromosomal locus that suppresses the lethality when harbored in a low copy-number plasmid, without restoring the synthase activity or phospholipid composition to normal. The locus was first recognized to suppress the conditional lethality of E. coli YA5512 (pgsA3) that harbored an unidentified mutation(s), allowing its growth in LB medium but not in media of lower osmolarities. The locus was then found to suppress the lethality of pgsA3 in wild-type E. coli W3110. This locus, named ypoP in the database, had 37% nucleotide identity with the E. coli mprA gene, but the amplification of mprA had no suppressive effect. Plasmid pPOP1 containing ypoP completely prevented the decrease in the amount of a porin protein, OmpF, in the outer membrane and also cell mucoidy caused by pgsA3. The mechanisms underlying these unusual effects are discussed in relation to a putative stress signal(s) generated by the acidic-phospholipid deficiency. 相似文献
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An autosomal recessive deafness mutant was discovered in our colony of Zucker (ZUC) rats. These mutants behave like shaker-waltzer
deafness mutants, and their inner ear pathology classifies them among neuroepithelial degeneration type of deafness mutants.
To determine whether this rat deafness mutation (−) defines a unique locus or one that has been previously described, we mapped
its chromosomal location. F2 progeny of (Pbrc:ZUC × BN/Crl) A/a B/b
H/h+/− F1 rats were scored for coat color and behavioral phenotypes. Segregation analysis indicated that the deafness locus might be
loosely linked with B on rat Chromosome (Chr) 5 (RNO5). Therefore, 40 −/− rats were scored for BN and ZUC alleles at four additional loci, D5Mit11, D5Mit13, Oprd1, and Gnb1, known to map to RNO5 or its homolog, mouse Chr 4 (MMU4). Linkage analysis established the gene order (cM distance) as D5Mit11–(19.3)–B–(17.9)–D5Mit13–(19.2)–Oprd1–(21.5) − (1.2) Gnb1, placing the deafness locus on distal RNO5. The position of the deafness locus on RNO5 is similar to that ofjerker (je) on MMU4; the phenotypes and patterns of inheritance of the deafness mutation and je are also similar. It seems likely that the mutation affects the rat homolog of je. The rat deafness locus should, therefore, be named jerker and assigned the gene symbol Je.
Received: 13 June 1995 / Accepted: 4 January 1996 相似文献