RENAL PATHOLOGY AND MORPHOMETRIC STUDIES ON NATURAL HISTORY OF BXSB LUPUS MICE

Abstract

IntroductionBXSB is a prototypic murine model for Systemic Lupus Erythematosus manifested. Although few scoring systems have been reported in the literature, there has been no consensus on how to evaluate murine lupus nephritis.MethodsPost mortem renal tissue sections from male BXSB mice at 10, 20 , 30, 40 and 50 weeks of age (collectively n=45 ) were evaluated for histopathology on H&E, and PAS staining. Quantitative measurements of glomerular cell count, glomerular tuft area, and glomerular sclerosis areas were obtained on an average of 10 glomeruli per mouse by using computerized image analysis provided by Nikon. Controls were age matched male C57Bl/6 (n=3 per group) or female BXSB (n=3 at 30 weeks) mice.ResultsThere is progressive increase in glomerular cellularity and tuft size with age in mice at 10 and 20 weeks of age, compared to controls. Sclerosis was evident starting at 30 weeks. Four major step of progression were appreciated: 1) increased glomerular cellularity with increased glomerular size at 10th and 20th week of age; 2) expansion of matrix at 20 to 30 weeks of age; 3) progressive sclerosis with corresponding decreased cell counts, in mice at 30 to 40 weeks of age; and 4) end‐stage disease with pan‐sclerosis and glomerular obliteration in older mice.ConclusionsThe renal pathology in BXSB follows a predictable pattern that resembles human renal pathology. Computerized quantitative measurement of glomerular cell counts, tuft size and extent of sclerosis is a reliable objective tool to study lupus nephritis in mouse models and effect of experimental treatment options.