Search results for "Exons"

showing 10 items of 197 documents

AAV Vector–mediated RNAi of Mutant Huntingtin Expression Is Neuroprotective in a Novel Genetic Rat Model of Huntington's Disease

2008

We report the characterization of a new rapid-onset model of Huntington's disease (HD) generated by adeno-associated virus (AAV) vector–mediated gene transfer of N-terminal huntingtin (htt) constructs into the rat striatum. Expression of exon 1 of mutant htt containing 70 CAG repeats rapidly led to neuropathological features associated with HD. In addition, we report novel data relating to neuronal transduction of AAV vectors that modulated the phenotype observed in this model. Quantitative reverse transcriptase–polymerase chain reaction (RT–PCR) revealed that AAV vector–mediated expression in the striatum increased by >100-fold as compared to the endogenous htt level. Moreover, AAV vectors…

HuntingtinvirusesGenetic VectorsNerve Tissue ProteinsSubstantia nigraBiologyArticleViral vectorHuntington's diseaseRNA interferenceDrug DiscoverymedicineHuntingtin ProteinGeneticsAnimalsHumansMolecular BiologyNeuronsPharmacologyHuntingtin ProteinGene knockdownReverse Transcriptase Polymerase Chain ReactionNeurodegenerationNuclear ProteinsExonsGenetic TherapyDependovirusmedicine.diseaseMolecular biologyCorpus StriatumRatsHuntington DiseaseNeuroprotective AgentsPhenotypenervous systemMolecular MedicineRNA InterferenceMolecular Therapy
researchProduct

Polymorphism of mytilin B mRNA is not traslated into mature peptide

2008

Diversity of mRNAs from mytilin B, one of the five mytilins identified in the Mediterranean mussel, Mytilus galloprovincialis, has been investigated from circulating hemocytes. One mussel expressed simultaneously two to ten different mytilin B mRNAs as observed in denaturing gradient gel electrophoresis (DGGE), defining 10 individual DGGE patterns (named A to J) within the mussels from Messina, Sicily (Italy). Three patterns accounted for 79% of the individuals whereas other patterns were found in only 2-7% of the 57 analyzed mussels. Base mutations were observed at specific locations, mainly within COOH-terminus and 3'UTR, leading to 36 nucleotide sequence variants and 21 different coding …

ImmunologyMolecular Sequence DataAntimicrobial peptide Defensin mRNA polymorphism DGGE.Evolution MolecularExonchemistry.chemical_compoundOpen Reading FramesAnimalsAmino Acid SequenceRNA MessengerSelection GeneticMolecular BiologyGenePeptide sequencePhylogenyGeneticsElectrophoresis Agar GelMytilusGenomePolymorphism GeneticbiologyBase SequenceMytilinNucleic acid sequenceIntronExonsbiology.organism_classificationMolecular biologyMytiluschemistryGene Expression RegulationProtein BiosynthesisPeptidesTemperature gradient gel electrophoresisAntimicrobial Cationic Peptides
researchProduct

Complete coding nucleotide sequence of cDNA for the class II RT1.B beta I chain of the Lewis rat.

1991

We have established the first full length cDNA clone for the beta light chain of the MHC class II alpha, beta heterodimer (isotype RT1.B) of the rat. Clone pLR beta 118 was obtained from a self-primed lambda gt10 cDNA library of IFN-tau treated bone marrow-derived macrophages of the Lewis rat. Subcloning of pLR beta 118 into a transcription vector with subsequent in vitro transcription and translation using the reticulocyte lysate system in the presence of microsomes followed by immunoprecipitation with mAb OX6 and two-dimensional gel electrophoresis revealed the intact RT1.B beta I-chain.

ImmunoprecipitationMolecular Sequence DataBiophysicsBone Marrow CellsBiologyImmunoglobulin light chainTransfectionBiochemistryReticulocyteStructural BiologyTranscription (biology)Complementary DNAHistocompatibility AntigensGeneticsmedicineAnimalsElectrophoresis Gel Two-DimensionalAmino Acid SequenceCells CulturedBase SequencecDNA libraryMacrophagesNucleic acid sequenceDNAExonsMolecular biologyRatsmedicine.anatomical_structureSubcloningRats Inbred LewBiochimica et biophysica acta
researchProduct

p53 mutations are common in human papillomavirus type 38-positive non-melanoma skin cancers

2004

Copyright © 2003 Elsevier Ireland Ltd. All rights reserved.

Keratinocytesp53Human papillomavirusCancer ResearchE6 proteinSkin NeoplasmsNon-melanoma-skin cancerImmunoblottingmedicine.disease_causePolymerase Chain ReactionmedicineAnimalsHuman papillomavirusCodonPapillomaviridaeGeneCells CulturedE6integumentary systemReverse Transcriptase Polymerase Chain Reactionbusiness.industryDNAExonsCervical cellsFibroblastsGenes p53Coculture TechniquesRatsRetroviridaeOncologyMutationCancer researchCarcinogenesisbusinessNon melanomaCancer Letters
researchProduct

Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III)

1998

Nitric oxide synthase (NOS) exists in three established isoforms. NOS I (NOS1, ncNOS) was originally discovered in neurons. This enzyme and splice variants thereof have since been found in many other cells and tissues. NOS II (NOS2, iNOS) was first identified in murine macrophages, but can also be induced in many other cell types. NOS III (NOS3, ecNOS) is expressed mainly in endothelial cells. Whereas NOS II is a transcriptionally regulated enzyme, NOS I and NOS III are considered constitutively expressed proteins. However, evidence generated in recent years indicates that these two isoforms are also subject to expressional regulation. In view of the important biological functions of these …

LipopolysaccharidesGene isoformNitric Oxide Synthase Type IIITranscription GeneticNOS1Nitric Oxide Synthase Type IBiochemistryTranscription (biology)GeneticsTranscriptional regulationAnimalsHumansRNA MessengerGrowth SubstancesMolecular BiologyTranscription factorRegulation of gene expressionPolymorphism GeneticbiologyChemistryChromosome MappingLysophosphatidylcholinesNitric Oxide Synthase Type IIIEstrogensExonsCell biologyIsoenzymesLipoproteins LDLOxygenNitric oxide synthaseGene Expression Regulationbiology.proteinCytokinesNitric Oxide SynthaseGene DeletionBiotechnologyThe FASEB Journal
researchProduct

Heterozygous HMGB1 loss-of-function variants are associated with developmental delay and microcephaly

2021

International audience; 13q12.3 microdeletion syndrome is a rare cause of syndromic intellectual disability. Identification and genetic characterization of patients with 13q12.3 microdeletion syndrome continues to expand the phenotypic spectrum associated with it. Previous studies identified four genes within the approximately 300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. To date, no patients carrying a sequence-level variant or a single gene deletion in HMGB1 or KATNAL1 have been described. Here we report six patients with loss-of-function variants involving HMGB1 and who had phenotypic features similar to the previously described 13q12.3 m…

Male0301 basic medicineHeterozygoteMicrocephalyAdolescentDNA Copy Number VariationsLanguage delay[SDV]Life Sciences [q-bio]KaryotypeInheritance Patternschemical and pharmacologic phenomena030105 genetics & heredityBiologydysmorphic featuresloss of function mutation03 medical and health sciencesExome SequencingIntellectual disabilityGeneticsmedicineHumansGenetic Predisposition to DiseaseHMGB1 ProteinChildGeneGenetic Association StudiesIn Situ Hybridization FluorescenceGenetics (clinical)Loss functionGeneticsHMGB1FaciesExonsdevelopmental disabilitiesMicrodeletion syndromemedicine.diseasePhenotypePhenotype030104 developmental biologyChild PreschoolMicrocephalyFemaleHaploinsufficiency
researchProduct

Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis

2015

We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line. All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits. 64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7–10.9) and 5 months (95% CI 3.6–6.7) respectively (P = 0.012). No difference wa…

Male0301 basic medicineIndolesTime FactorsGIST; exon 11; imatinib; second line; sunitinibGastroenterologyExon 11Exon0302 clinical medicineSecond linehemic and lymphatic diseasesSunitinibMedicineAged 80 and overGiSTSunitinibExonsMiddle AgedProto-Oncogene Proteins c-kitOncology030220 oncology & carcinogenesisDisease ProgressionImatinib MesylateFemaleResearch PaperGISTmedicine.drugAdultmedicine.medical_specialtyGastrointestinal Stromal TumorsAntineoplastic AgentsDisease-Free Survival03 medical and health sciencesInternal medicineHumansPyrrolesAgedRetrospective StudiesSecond lineSecond line treatmentDose-Response Relationship Drugbusiness.industryRetrospective cohort studyImatinibSurgery030104 developmental biologyImatinib mesylateMutationImatinibbusinessOncotarget
researchProduct

Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder

2017

AbstractGenetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. We systematically evaluated PMMs by leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection. We found evidence that 11% of published single nucleotide variant (SNV)de novomutations are potentially PMMs. We then developed a robust SNV PMM calling approach that leverages complementary callers, logistic regression modeling, and additional heuristics. Using this approach, we recalled SNVs and found that 22% ofde novomutations like…

Male0301 basic medicineProbandZygoteautism spectrum disorderSYNGAP1Biologypostzygoticmedicine.disease_causeArticleGermlineCohort Studies03 medical and health sciencessplicing0302 clinical medicineNeurodevelopmental disorderGermline mutationDatabases GeneticGeneticsmedicineHumansMissense mutationGenetic Predisposition to DiseaseChild[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human geneticsGenetics (clinical)030304 developmental biologyGenetics0303 health sciencesMutationneurodevelopmentsomaticGenetic VariationExonsmedicine.disease030104 developmental biologymosaicism[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human geneticsAutism spectrum disorderCHD2AutismFemalemutation030217 neurology & neurosurgeryexome
researchProduct

Identification and characterization of a gene encoding a putative mouse Rho GTPase activating protein gene 8, Arhgap8.

2003

Rho GTPase activating proteins promote the intrinsic GTP hydrolysis activity of Rho family proteins. We isolated a putative mouse ortholog of the human Rho GTPase activating protein 8, ARHGAP8. The open reading frame encodes a peptide of 387 amino acids with high homology to human ARHGAP8 in its N-terminal domain. Both radiation hybrid mapping and fluorescent in situ hybridization localized the gene to mouse chromosome 15E. The 23 kb genomic Arhgap8 sequence consists of eight exons and seven introns. Northern blot and RT-PCR analyses showed that a transcript of approximately 1.9 kb is ubiquitously expressed in various adult mouse tissues with particularly strong expression in kidney.

MaleARHGAP8DNA ComplementaryGTPase-activating proteinMolecular Sequence DataGene ExpressionGTPaseBiologyExonMiceGene expressionGeneticsAnimalsAmino Acid SequenceRNA MessengerCloning MolecularGenePeptide sequenceIn Situ Hybridization FluorescenceRadiation Hybrid MappingBase SequenceSequence Homology Amino AcidGTPase-Activating ProteinsChromosome MappingGeneral MedicineExonsSequence Analysis DNABlotting NorthernMolecular biologyIntronsOpen reading frameGenesSequence AlignmentGene
researchProduct

Soft tissue Ewing sarcoma--peripheral primitive neuroectodermal tumor with atypical clear cell pattern shows a new type of EWS-FEV fusion transcript.

2000

This study describes a new case of Ewing sarcoma (ES)-peripheral primitive neuroectodermal tumor (pPNET) with unusual phenotype and fusion gene structure. The tumor located in the inguinal area of a 15-year-old boy showed a highly aggressive behavior with hematogenous metastases after intensive chemotherapy and bone marrow transplant, causing death 28 months after diagnosis. The tumor displayed a clear cell pattern, and several neuroectodermal markers proved positive both in the original tumor and in xenografts. This neuroectodermal character was confirmed by electron microscopy. Moreover, cytogenetically the tumor has an unusual chromosomal rearrangement, t(2;22)(q13;q22,t(3;18)(p21;q23); …

MaleAdolescentOncogene Proteins FusionChromosomes Human Pair 22Transplantation HeterologousMice NudeSoft Tissue NeoplasmsChromosomal rearrangementSarcoma EwingBiologyGroinTranslocation GeneticPathology and Forensic MedicineFusion geneExonMiceFatal OutcomemedicineTumor Cells CulturedAnimalsHumansNeuroectodermal Tumors PrimitiveNeoplasm MetastasisMolecular BiologyPeripheral Primitive Neuroectodermal TumorReverse Transcriptase Polymerase Chain ReactionCell BiologyExonsmedicine.diseasePrognosisCombined Modality TherapyNeoplasm ProteinsFusion transcriptPrimitive neuroectodermal tumorChromosomes Human Pair 2KaryotypingCancer researchDisease ProgressionSarcomaClear cellDiagnostic molecular pathology : the American journal of surgical pathology, part B
researchProduct