MeCP2 Transgenic Mouse as A New Disease Model for Neuropsychiatric Lupus

dc.contributor.advisorWu, Tianfu
dc.contributor.committeeMemberMohan, Chandra
dc.contributor.committeeMemberShevkoplyas, Sergey S.
dc.contributor.committeeMemberZhang, Yingchun
dc.contributor.committeeMemberSalim, Samina
dc.creatorLi, Yaxi
dc.date.accessioned2021-10-01T16:53:30Z
dc.date.createdMay 2021
dc.date.issued2021-05
dc.date.submittedMay 2021
dc.date.updated2021-10-01T16:53:34Z
dc.description.abstractNeuropsychiatric lupus (NPSLE) impacts a large cohort of lupus patients and is an important driver of disease morbidity and mortality. The complexity and heterogeneity of clinical presentations impede the investigation of disease etiology directly in patients. Several mouse models have been used for the NPSLE study, however, there is no unifying model to fully represent the disease pathogenesis yet. This study aims to determine whether C57BL/6 mice transgenic for human MeCP2 (B6.MECP2Tg1) could serve as a new mouse model for NPSLE, which could be used for uncovering disease mechanisms and the identification of novel therapeutic targets. First, we found MeCP2 protein expression level was significantly increased in the brain and spleen in a spontaneous lupus mouse model MRL/lpr as well as a female B6.MECP2Tg1 mice, when compared to B6. In addition, the B6.MECP2Tg1 transgenic mice exhibited elevated proteinuria, and increased autoantibody production including total IgG, IgG anti-dsDNA antibody and other autoantibodies as revealed by an autoantigen array. Furthermore, immunofluorescence analysis revealed that IgG deposition and macrophage infiltration were more severe in the kidney of female B6.MECP2Tg1 compared to B6. Interestingly, the effector memory T cells, activated germinal center B cells and plasma B cells were markedly increased in the female B6.MeCP2Tg1 mice. In the neuropsychiatric aspects, B6.MECP2Tg1 mice exhibited anxiety and depression-like behavior, as well as cognitive disorders at young age. These abnormal behaviors may be explained by the altered neurogenesis and inflammation in the hippocampus, immune cell infiltration in the choroid plexus, as well as the disrupted blood-brain barrier (BBB) and activated microglia, as demonstrated by immunofluorescence microscopy. Collectively, this work demonstrates that B6.MECP2Tg1 mice exhibit lupus-like phenotypes as well as clear CNS dysfunctions, suggesting it may represent a new animal model for NPSLE.
dc.description.departmentBiomedical Engineering, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10657/8294
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectNPSLE, mouse model, MeCP2, autoimmune, behavior, neurogenesis, hippocampus, blood-brain barrier
dc.titleMeCP2 Transgenic Mouse as A New Disease Model for Neuropsychiatric Lupus
dc.type.dcmiText
dc.type.genreThesis
local.embargo.lift2023-05-01
local.embargo.terms2023-05-01
thesis.degree.collegeCullen College of Engineering
thesis.degree.departmentBiomedical Engineering, Department of
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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