Featured Publications
Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice
Roy S, Li Z, Guo Z, Long K, Rehrl S, Tian X, Dong K, Besse W. Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice. Journal Of The American Society Of Nephrology 2023, 34: 1521-1534. PMID: 37332102, PMCID: PMC10482070, DOI: 10.1681/asn.0000000000000164.Peer-Reviewed Original ResearchConceptsUnfolded protein responseAutosomal dominant tubulointerstitial kidney diseaseAutosomal dominant polycystic kidney diseasePolycystin-1Autosomal-dominant polycystic kidney diseaseProtein responseTubulointerstitial kidney diseaseKidney diseaseRenal failureRenal failure in adulthoodPolycystic kidney diseaseUnfolded protein response activationFull-length proteinProteins polycystin-1C-terminal fragmentCystic kidneysSite of maturationCystic kidney dysplasiaKidney disease pathogenesisHeterozygous inactivating mutationsHsp40 cochaperonesEndoplasmic reticulumMouse model studiesConditional allelesDNAJB11Isolated polycystic liver disease genes define effectors of polycystin-1 function
Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. Journal Of Clinical Investigation 2017, 127: 1772-1785. PMID: 28375157, PMCID: PMC5409105, DOI: 10.1172/jci90129.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCalcium-Binding ProteinsCell Line, TransformedCystsEndoplasmic ReticulumFemaleGenome-Wide Association StudyGlucosidasesGlucosyltransferasesHeterozygoteHumansIntracellular Signaling Peptides and ProteinsLiver DiseasesMaleMembrane ProteinsMiceMolecular ChaperonesMutationRNA-Binding ProteinsSEC Translocation ChannelsTRPP Cation ChannelsConceptsPolycystin-1 functionPolycystin-1Protein biogenesis pathwaysGenome-wide basisPolycystic liver diseaseLoss-of-function mutationsWhole-exome sequencingHeterozygous loss-of-function mutationsBiogenesis pathwayLoss of functionAdditional genesDisease genesGene productsCell line modelsCandidate genesExome sequencingEndoplasmic reticulumCausative genesFunction mutationsGenesAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseSec63Defective maturationKidney cystsAdult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease.
Besse W, Roosendaal C, Tuccillo L, Roy SG, Gallagher AR, Somlo S. Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease. Kidney360 2020, 1: 1068-1076. PMID: 33554127, PMCID: PMC7861569, DOI: 10.34067/kid.0002522020.Peer-Reviewed Original ResearchConceptsAutosomal recessive polycystic kidney diseaseSomatic second-hit mutationsAutosomal dominant polycystic kidney diseaseSecond-hit mutationsPolycystic liver diseaseLiver phenotypePolycystic kidney diseaseBile duct homeostasisSecond hit mutationLiver cystsLiver diseaseKidney diseaseCyst formationGenetic interactionsPattern of inheritanceDisease genesRecessive polycystic kidney diseaseGermline inheritanceDominant polycystic kidney diseaseDuctal plate formationWeeks of ageRecessive genotypeSubset of adultsSomatic mutationsPlate format
2022
An update on ductal plate malformations and fibropolycystic diseases of the liver
Mirza H, Besse W, Somlo S, Weinreb J, Kenney B, Jain D. An update on ductal plate malformations and fibropolycystic diseases of the liver. Human Pathology 2022, 132: 102-113. PMID: 35777701, DOI: 10.1016/j.humpath.2022.06.022.Peer-Reviewed Original ResearchConceptsDuctal plate malformationLiver diseaseAdult polycystic liver diseaseAutosomal dominant polycystic kidneyFibropolycystic liver diseaseIsolated liver involvementCongenital hepatic fibrosisPolycystic liver diseaseVon Meyenburg complexesGenetic underpinningsMultiple clinical phenotypesFibropolycystic diseasePortal hypertensionCaroli's diseaseLiver involvementLiver cystsMeyenburg complexesHepatic fibrosisFibrocystic lesionsHepatocellular malignanciesCyst enlargementAbnormal organ developmentPolycystic kidneysAnimal modelsHepatocellular malignancy
2008
Ectopic expression of peripheral-tissue antigens in the thymic epithelium: Probabilistic, monoallelic, misinitiated
Villaseñor J, Besse W, Benoist C, Mathis D. Ectopic expression of peripheral-tissue antigens in the thymic epithelium: Probabilistic, monoallelic, misinitiated. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 15854-15859. PMID: 18836079, PMCID: PMC2572966, DOI: 10.1073/pnas.0808069105.Peer-Reviewed Original ResearchConceptsPeripheral-tissue antigensMedullary epithelial cellsPeripheral tissue antigensPta geneSelf-tolerant T cell repertoireTranscription start sitePeripheral cellsThymic medullary epithelial cellsCoexpression of genesT cell repertoireRepertoire of antigensEpithelial cell lineagesStart siteTranscriptional regulationBiallelic transcriptionThymic epitheliumPresenting antigensEctopic expressionCell repertoireGenesAIRE functionEpithelial cellsAntigenSingle-cell PCRCell lineages
2005
Variation in IL-1β gene expression is a major determinant of genetic differences in arthritis aggressivity in mice
Ohmura K, Johnsen A, Ortiz-Lopez A, Desany P, Roy M, Besse W, Rogus J, Bogue M, Puech A, Lathrop M, Mathis D, Benoist C. Variation in IL-1β gene expression is a major determinant of genetic differences in arthritis aggressivity in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 12489-12494. PMID: 16113081, PMCID: PMC1194932, DOI: 10.1073/pnas.0504325102.Peer-Reviewed Original ResearchConceptsInbred strainsWhole-genome scanQuantitation of transcriptsInterleukin-1 gene familyConventional inbred strainsWild-derived strainsComplex genetic controlSequence haplotypesGenomic regionsGenetic lociNoncoding polymorphismsCandidate genesGenetic analysisGenetic differencesBALB/c haplotypeGenetic controlGene expressionIL-1B gene expressionBreeding strategiesBreeding schemesIL1B geneGenesSerum-transfer arthritisStrainHigh-responder BALB/c