An Antibiotic-Responsive Mouse Model of Fulminant Ulcerative Colitis 英文参考文献.docVIP

o PL SMEDICINE AnAntibiotic-ResponsiveMouseModel ofFulminantUlcerativeColitis Silvia S.Kang1,Seth M.Bloom1,Lyse A.Norian1,Michael J.Geske1,Richard A.Flavell2,3,Thaddeus S.Stappenbeck1*{ Paul M.Allen1*{ , 1DepartmentofPathologyandImmunology,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,2SectionofImmunobiology,Yale University School of Medicine, New Haven, Connecticut, United States of America, 3 Howard Hughes Medical Institute,Yale University School ofMedicine, New Haven, Connecticut,UnitedStatesofAmerica Funding:Thisworkwassupported bygrantsfromtheNational InstitutesofHealth(NIH)andbya CancerResearchInstitute predoctoralfellowship(SSK).The fundershadnoroleinthestudy design,datacollection,decisionto publishorpreparationofthe manuscript. ABSTRACT Background Theconstellationofhumaninflammatoryboweldisease(IBD)includesulcerativecolitisand Crohn’sdisease,whichbothdisplayawidespectrumintheseverityofpathology.Onetheoryis thatmultiplegenetichitstothehostimmunesystemmaycontributetothesusceptibilityand severity of IBD. However, experimental proof of this concept is still lacking. Several genetic mousemodelsthateachrecapitulatesomeaspectsofhumanIBDhaveutilizedasinglegene defect to induce colitis. However, none have produced pathology clearly distinguishable as eitherulcerativecolitisorCrohn’sdisease,inpartbecausenoneofthemreproducethemost severeformsofdiseasethatareobservedinhumanpatients.ThislackofsevereIBDmodelshas posed a challenge for research into pathogenic mechanisms and development of new treatments. We hypothesized that multiple genetic hits to the regulatory machinery that normallyinhibitsimmuneactivationintheintestinewouldgeneratemoresevere,reproducible pathologythatwouldmimiceitherulcerativecolitisorCrohn’sdisease. CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. AcademicEditor:LudvigM.Sollid, UniversityofOslo,Norway Citation:KangSS,BloomSM,Norian LA,GeskeMJ,FlavellRA,etal.(2008) Anantibiotic-responsivemo