Title

Abrogated AID Function Prolongs Survival and Diminishes Renal Pathology in the BXSB Mouse Model of Systemic Lupus Erythematosus.

Document Type

Article

Publication Date

3-1-2020

Keywords

JMG, Animals, B-Lymphocyte Subsets, CRISPR-Cas Systems, Cytidine Deaminase, Disease Models, Animal, Lupus Erythematosus, Systemic, Mice, Mice, Knockout

JAX Source

J Immunol 2020 Mar 1; 204(5):1091-1100

PMID

31988182

DOI

https://doi.org/10.4049/jimmunol.1900501

Abstract

Almost a decade has passed since the approval of belimumab, an mAb directed against B lymphocyte stimulation and the first targeted therapy approved for systemic lupus erythematous (SLE) in over 50 y. Although well tolerated, the efficacy of belimumab remains limited and is not labeled for patients suffering from nephritis, the leading cause of patient mortality. We sought to explore alternative targets of autoreactive B lymphocytes through manipulation of affinity maturation. The BXSB/MpJ mouse, a well-established model of human SLE, develops elevated antinuclear Abs and immune complex-mediated nephritis along with other manifestations of SLE-like disease. To limit interfering with critical background genetics, we used CRISPR-Cas9 to disrupt activation-induced cytidine deaminase (AID;

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