Histopathological characteristics of the kidney in recombinant inbred mice established from MRL/lpr x AKR crossing. Dissociation of severity of lupus nephritis from the degree of lymphadenopathy.
Recombinant inbred (RI) lines were established from (MRL/lpr x AKR) crosses in order to analyze the role of the lpr gene and the participation of background genes in the lymphoproliferation and the development of lupus glomerulonephritis (LGN). In this study, six lines were used to compare with MRL/lpr and AKR mice. Lymphadenopathy was present in four lines (A-22, A-31 b, A-31 e and C-12) but absent in the other two (A-21 and C-21). The degree of lymphoproliferation varied between individuals of the RI lines showing lymphadenopathy. On gross examinations, the most marked lymph node enlargement was seen in the A-31 b line, which resembled MRL/lpr mice in this respect; lymphadenopathy was least prominent in the C-12 line and intermediate degrees occurred in the A-22 and A-31 e lines. Like MRL/lpr mice, deaths in the RI lines were due to LGN; however, in the lines with lymphadenopathy, 50% mortalities occurred a few weeks later than in MRL/lpr mice. The kidneys were examined histologically for proliferative, exudative, extracapillary and membranous changes in the glomeruli. The glomerular lesions in the A-22, A-31 b and A-31 e lines closely resembled those in MRL/lpr mice, but in the C12 line in which lymph node enlargement was least apparent, the histological abnormalities were significantly more severe. Of the lines without lymphadenopathy, histopathological examination showed obvious renal abnormalities in the A-21 line but none in the C-21 line or in AKR mice. From these findings it appears that there are autosomal genes which affect the expression of the lpr gene and thus modify the development of LGN and lymphoproliferation.
Makino
M
M
Laboratory of Immunology, Niigata University School of Medicine, Japan.
Morita
T
T
Fujiwara
M
M
D000818:Animals; D003433:Crosses, Genetic; D007668:Kidney / Q000473:pathology*; D008181:Lupus Nephritis / Q000235:genetics* / Q000473:pathology; D008206:Lymphatic Diseases / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*