Characterization of a NZM2328 derived recombinant congenic strain which has an 8Mb C57L/J fragment on distal chromosome 1

Abstract

NZM2328 mice develop severe proteinuria and glomerulonephritis (GN) with a gender bias towards females and are used as a spontaneous murine SLE model. Previously, a recombinant line NZM2328.C57L/Jc1 was characterized in which a 26Mb C57L/J chr. 1 fragment was introgressed onto NZM2328. These female mice have no ANA, anti‐dsDNA Ab's, or GN. We have further generated a novel recombinant congenic strain R27, in which an 8Mb C57L/J chr. 1 fragment was introgressed onto NZM2328 background. Severe proteinuria and ANA were inhibited in R27 female mice at 12 months of age. However, R27 sera stained normal kidney sections, indicating the presence of Ab's against the kidney. Immune complex (IC) deposits were detected in kidneys of 12‐month‐old as well as 5‐month‐old R27 female mice. Kidney histology showed acute GN without chronic GN. In addition, mononuclear cell infiltration into glomeruli was detected. These results support the hypothesis that acute GN need not proceed to chronic GN. Acute and chronic GN may be caused by two distinct mechanisms. Also, it is apparent that autoantibodies other than those for dsDNA are responsible for the IC deposits. Thus, R27 strain is a valuable model to study the pathogenesis and genetics of SLE, suggesting that some of the genes within this 8Mb region may be important for resistance to end organ damage and that these genes may be distinct from those promoting innate and adaptive immunity.