A comprehensive phenotyping program for the MRL-lpr mouse lupus model

Abstract

Abstract MRL/MpJ-Faslpr/J (MRL-lpr) mice develop an autoimmune disease resembling systemic lupus erythematosus, a disease affecting > 1.5 million Americans. The causative mutation, Faslpr, promotes survival of self-reactive lymphocytes, leading to immune proliferation, lymphadenopathy, emergence of anti-DNA antibodies, and fatal immune complex glomerulonephrosis. Like all spontaneous autoimmunity models, MRL-lpr colonies are susceptible to inadvertent selective pressure when mice with absent or delayed phenotypes are bred. We will explain a program for promoting genetic and phenotypic integrity within MRL-lpr breeding colonies. In addition to confirmation of genetic background and Faslpr genotype, breeder phenotypes were assessed at the conclusion of the breeding period. White blood cell counts (WBC) were used to measure lymphoproliferation: at 17 weeks of age, median WBC (103 cells/μL) was 14.2 for females (range = 3.4 – 97.3; N=155) and 10.5 for males (range = 3.7 – 51.4; N=125). Urinalysis to characterize renal damage at 18 weeks of age showed a median albumin/creatinine ratio of 623 for females (range = 1 – 22806; N=163) and 95 for males (range = 1 – 6013; N=123). Median spleen weights (grams) at 18 weeks of age were 0.5464 in females (range = 0.1112 – 2.1348; N=177) and 0.4410 in males (range = 0.2078 – 1.5516; N=135). We will describe a scoring system for clinical signs present at gross necropsy, including appearance of fur/skin, lymph nodes, and organs. We will show that phenotypic integrity can be ensured over time by breeding mice from lineages showing optimal disease development criteria. This program has value beyond breeder assessment, as it can be applied to MRL-lpr mice on study and at conclusion.