CNS lupus in MRL/Faslpr mice (130.15)

Abstract Neuropsychiatric involvement is common in patients with SLE; however, its etiology is incompletely understood. Fas-deficient MRL/Faslpr (MRL/Faslpr) mice develop a spontaneous autoimmune disease that is similar to human SLE, including cognitive and neurological deficits. We hypothesized that autoantibodies in MRL/Faslpr mice may promote central nervous system (CNS) injury. Antibody (Ig) deposition in the CNS and structural abnormalities were assessed by immunofluorescent microscopy and diffusion tensor imaging (DTI) using a 11.7T system. At 20 weeks of age, MRL/Faslpr mice exhibited dense deposits of IgG in the choroid plexus, whereas several other control mice, including Fas-intact MRL mice, Fas-deficient C57BL6/Faslpr mice, and membrane only IgM-transgenic MRL/Faslpr mice (B cell-intact, but incapable of Ig secretion) did not reveal IgG staining, suggesting spontaneous Ig entry into the CNS in this lupus-prone mouse. DTI analysis demonstrated that MRL/Faslpr mice exhibited significantly increase in dorsal-ventral directional anisotropy in the hippocampus, compared to other control mice, suggesting these mice may have a structural abnormality in the hippocampus. Future work will focus on the role of Toll-like receptors in the Ig deposition and subsequent DTI alteration at distal regions of hippocampus in the MRL/Faslpr mice. Funding sources: Arthritis Investigator Award and Arthritis Innovative Grant, Arthritis Foundation