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dc.contributor.authorFlanagan, SE
dc.contributor.authorDe Franco, E
dc.contributor.authorLango Allen, H
dc.contributor.authorZerah, M
dc.contributor.authorAbdul-Rasoul, MM
dc.contributor.authorEdge, JA
dc.contributor.authorStewart, H
dc.contributor.authorAlamiri, E
dc.contributor.authorHussain, K
dc.contributor.authorWallis, S
dc.contributor.authorde Vries, L
dc.contributor.authorRubio-Cabezas, O
dc.contributor.authorHoughton, JA
dc.contributor.authorEdghill, EL
dc.contributor.authorPatch, AM
dc.contributor.authorEllard, Sian
dc.contributor.authorHattersley, Andrew T.
dc.date.accessioned2014-06-23T11:18:15Z
dc.date.issued2014-01-07
dc.description.abstractUnderstanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipDiabetes UKen_GB
dc.description.sponsorshipEuropean Community’s Seventh Framework Programme (FP7/2007-2013)en_GB
dc.identifier.citationCell Metabolism, 2014, Vol. 19, Issue 1, pp. 146 - 154en_GB
dc.identifier.doi10.1016/j.cmet.2013.11.021
dc.identifier.grantnumber098395/Z/12/Z
dc.identifier.urihttp://hdl.handle.net/10871/15081
dc.language.isoenen_GB
dc.publisherElsevieren_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/24411943en_GB
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S1550413113004920en_GB
dc.rights©2014 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_GB
dc.subjectAdolescenten_GB
dc.subjectAmino Acid Sequenceen_GB
dc.subjectAnimalsen_GB
dc.subjectChild, Preschoolen_GB
dc.subjectDiabetes Mellitusen_GB
dc.subjectFemaleen_GB
dc.subjectHomeodomain Proteinsen_GB
dc.subjectHomozygoteen_GB
dc.subjectHumansen_GB
dc.subjectInfanten_GB
dc.subjectInfant, Newbornen_GB
dc.subjectMaleen_GB
dc.subjectMiceen_GB
dc.subjectMolecular Sequence Dataen_GB
dc.subjectMutationen_GB
dc.subjectPancreasen_GB
dc.subjectPhenotypeen_GB
dc.subjectTranscription Factorsen_GB
dc.titleAnalysis of transcription factors key for mouse pancreatic development establishes NKX2-2 and MNX1 mutations as causes of neonatal diabetes in manen_GB
dc.typeArticleen_GB
dc.date.available2014-06-23T11:18:15Z
dc.identifier.issn1550-4131
exeter.place-of-publicationUnited States
dc.descriptionnotes: PMCID: PMC3887257en_GB
dc.descriptionThis is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.en_GB
dc.identifier.journalCell Metabolismen_GB


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