Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis 英文参考文献.docVIP

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Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis 英文参考文献.doc

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Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis 英文参考文献

GeneExpressionProfilingofaMouseModelof PancreaticIsletDysmorphogenesis LauraWildingCrawford2.,ElizabethTweedieAbles2.,YoungAhOh1,BradenBoone2,ShawnLevy2, MaureenGannon1,2 * 1DepartmentofMedicine,DivisionofDiabetes,Endocrinology,andMetabolism,VanderbiltUniversityMedicalCenter,Nashville,Tennessee,UnitedStatesofAmerica, 2DepartmentofMolecularPhysiologyandBiophysics,VanderbiltUniversityMedicalCenter,Nashville,Tennessee,UnitedStatesofAmerica Abstract Background: In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despitethissuccess,manyofthefactorsnecessaryforproperisletmorphogenesisandfunctionremainuncharacterized. Previousstudieshaveshownthattransgenicover-expressionofthetranscriptionfactorHnf6specificallyinthepancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increasedindividualisletsize,increasednumberofperipheralendocrinecelltypes,andfailureofisletstomigrateawayfrom the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yetto be elucidated. Methodology/PrincipalFindings:WeexploitedthedysmorphicisletsinHnf6transgenicanimalsasatooltoidentifyfactors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expressionprofilesoflategestationandearlypostnataltotalpancreastissuefromwildtypeandHnf6transgenicanimals. HerewereporttheidentificationofgeneswithanalteredexpressioninHnf6transgenicanimalsandhighlightfactorswith potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodelingandproliferationwerefoundtobealteredinHnf6transgenicpancreata,revealingspecificcandidatesthatcan nowbeanalyzeddirectlyfortheirroleintheseprocessesduringisletdevelopment. Conclusions/Significance:Thisstudyprovidesauniquedatasetthatcanactasastartingpointforotherinvestigatorsto exploretheroleofthei