Cellular and animal models for facioscapulohumeral muscular dystrophy
DeSimone AM, Cohen J, Lek M, Lek A. Cellular and animal models for facioscapulohumeral muscular dystrophy. Disease Models & Mechanisms 2020, 13: dmm046904. PMID: 33174531, PMCID: PMC7648604, DOI: 10.1242/dmm.046904.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsFacioscapulohumeral muscular dystrophyMicrosatellite repeat arraysNon-primate animalsRepeat arrayFSHD pathologyCellular pathwaysChromosome 4Myogenic differentiationExpression patternsMosaic expression patternMuscular dystrophyNew disease modelsHuman diseasesCellular modelMolecular factorsHumeral musclesSkeletal muscleDisease modelsMisexpressionDUX4GenesDrug candidatesTransgenicDifferentiationPathwayApplying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy
Lek A, Zhang Y, Woodman KG, Huang S, DeSimone AM, Cohen J, Ho V, Conner J, Mead L, Kodani A, Pakula A, Sanjana N, King OD, Jones PL, Wagner KR, Lek M, Kunkel LM. Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy. Science Translational Medicine 2020, 12 PMID: 32213627, PMCID: PMC7304480, DOI: 10.1126/scitranslmed.aay0271.Peer-Reviewed Original ResearchConceptsGenome-wide CRISPRCellular hypoxia responseFacioscapulohumeral muscular dystrophyHypoxia responseCell deathTherapeutic discoveryGenome-wide perturbationsComplex genetic diseasesEmergence of CRISPRUnbiased genetic screeningSelection assaysGene-editing technologyDUX4 proteinCausal genesDUX4 expressionZebrafish modelEpigenetic changesProtein turnoverMuscular dystrophyCRISPRMyogenic lineDUX4Genetic diseasesGenesMechanistic understanding