Narrowing of the SLES1 Internal Reveals Complex Epistatic Interactions in the Suppression of Autoimmunity

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dc.contributor.advisorWakeland, Edward K.en
dc.creatorBelobrajdic, Katherine Annen
dc.date.accessioned2010-07-12T17:15:32Z
dc.date.available2010-07-12T17:15:32Z
dc.date.issued2010-05-14
dc.description.abstractSle1 is a potent susceptibility locus for spontaneous systemic autoimmunity derived from the NZM2410 mouse strain. The NZW-derived suppressive modifier locus, Sles1, specifically prevents the spontaneous loss in tolerance mediated by the B6.Sle1 congenic. Sles1 had previously been fine-mapped to a remarkably gene-rich region on murine chromosome 17 containing nearly 70 genes. A series of mouse strains were constructed with a variety of suppressive and non-suppressive variants of Sles1 on the B6.Sle1 genomic background which have revealed multiple layers of epistatic gene interactions within the Sles1 interval. Phenotyping of a truncated recombinant interval mapped the Sles1 phenotype to an approximately 638 KB segment, which combined with genomic and expression analysis, suggested Btnl2 and the H2 genes are strong candidates for Sles1. Finally, further characterization of the Sles1 interval has revealed an allele-specific and tissue-specific reduction of major histocompatibility complex (MHC) Class II molecules on the surface of B cells, as well as a possible role for follicular helper T cells in the development of Sle1-mediated autoimmunity. Understanding how Sles1 and other modifiers suppress systemic autoimmunity will reveal important insights for developing therapeutic strategies for systemic lupus eythematosus (SLE).en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc795795283
dc.identifier.urihttps://hdl.handle.net/2152.5/240
dc.language.isoenen
dc.subjectLupus Erythematosus, Systemicen
dc.subjectEpistasis, Geneticen
dc.subjectMiceen
dc.titleNarrowing of the SLES1 Internal Reveals Complex Epistatic Interactions in the Suppression of Autoimmunityen
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2010-05-14
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineImmunologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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