2024
Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Zhang C, Rehman M, Tian X, Pei S, Gu J, Bell T, Dong K, Tham M, Cai Y, Wei Z, Behrens F, Jetten A, Zhao H, Lek M, Somlo S. Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease. Nature Communications 2024, 15: 3698. PMID: 38693102, PMCID: PMC11063051, DOI: 10.1038/s41467-024-48025-6.Peer-Reviewed Original ResearchConceptsMouse models of autosomal dominant polycystic kidney diseaseModel of autosomal dominant polycystic kidney diseasePolycystin signalingAutosomal dominant polycystic kidney diseasePolycystin-1Polycystic kidney diseaseTreat autosomal dominant polycystic kidney diseaseGlis2Primary ciliaKidney tubule cellsSignaling pathwayMouse modelDominant polycystic kidney diseasePotential therapeutic targetTranslatomeAntisense oligonucleotidesKidney diseasePolycystinMouse kidneyFunctional effectorsCyst formationTherapeutic targetInactivationFunctional targetPharmacological targets
2023
P299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice
Huang S, Ma K, Cohen J, Ho V, Xu J, Gauthier L, O'Connor C, Ge L, Woodman K, Lek M. P299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice. Neuromuscular Disorders 2023, 33: s118. DOI: 10.1016/j.nmd.2023.07.209.Peer-Reviewed Original ResearchGene replacement therapyReplacement therapySkeletal muscleFKRP geneLeft ventricular cavity sizeEvidence of myocarditisHigh expressionLow ejection fractionVentricular cavity sizeAutosomal recessive disorderCardiac involvementEjection fractionInflammatory infiltrationCardiac statusCardiac outputFatal cardiotoxicityFatal myocarditisDosed miceInclusion criteriaHeart sectionsMouse modelDystrophic miceDystrophic pathologyFKRP mutationsPatientsNoncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis
Tenney A, Di Gioia S, Webb B, Chan W, de Boer E, Garnai S, Barry B, Ray T, Kosicki M, Robson C, Zhang Z, Collins T, Gelber A, Pratt B, Fujiwara Y, Varshney A, Lek M, Warburton P, Van Ryzin C, Lehky T, Zalewski C, King K, Brewer C, Thurm A, Snow J, Facio F, Narisu N, Bonnycastle L, Swift A, Chines P, Bell J, Mohan S, Whitman M, Staffieri S, Elder J, Demer J, Torres A, Rachid E, Al-Haddad C, Boustany R, Mackey D, Brady A, Fenollar-Cortés M, Fradin M, Kleefstra T, Padberg G, Raskin S, Sato M, Orkin S, Parker S, Hadlock T, Vissers L, van Bokhoven H, Jabs E, Collins F, Pennacchio L, Manoli I, Engle E. Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis. Nature Genetics 2023, 55: 1149-1163. PMID: 37386251, PMCID: PMC10335940, DOI: 10.1038/s41588-023-01424-9.Peer-Reviewed Original ResearchConceptsSingle-nucleotide variantsGATA2 expressionHereditary congenital facial paresisBranchial motor neuronsLoss of GATA3Temporal gene regulationRare Mendelian diseasesChromosome 3q21-q22Autosomal dominant disorderSilencing in vitroNoncoding variationNoncoding variantsFacial paresisMendelian diseasesGene regulationRegulatory regionsHeterozygous duplicationDominant disorderMouse modelReporter expressionType 1Efferent neuronsMotor neuronsGATA2In vivo
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