Mice with early onset of death (EOD) due to lupus glomerulonephritis

• Published in: Clinical and experimental immunology Vol. 116; no. 1; pp. 153 - 163
• Main Authors: HONDA, S., NEMOTO, K., MAE, T., KINJOH, K., KYOGOKU, M., KAWAMURA, H., MIYAZAWA, S., WEERASHINGHE, A., WATANABE, H., NARITA, J., KOYA, T., ARAKAWA, M., ABO, T.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.04.1999; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Acute Disease; Aging; Animals; Autoantibodies - blood; Biological and medical sciences; Blood Platelets - cytology; Breeding; BXSB mice; Crosses, Genetic; Cytotoxicity, Immunologic; Disease Models, Animal; DNA - immunology; Experimental and animal immunopathology. Animal models; Female; Immunopathology; Kidney - immunology; Kidney - pathology; Killer Cells, Natural; Leukocytes - cytology; Liver - cytology; Liver - immunology; lpr gene; lupus glomerulonephritis; Lupus Nephritis - genetics; Lupus Nephritis - mortality; Lymph Nodes - immunology; Lymphocyte Subsets; Lymphocytosis; Male; Medical sciences; Mice - genetics; Mice, Inbred MRL lpr; MRL‐lpr/lpr mice; myeloid cell infiltration; Original; Sex Characteristics; Spleen - immunology; TCRint cells; Glomerulonephritis; Animal model; Skin disease; Autoimmune disease; Kidney; Histopathology; Immunological investigation; Systemic disease; T-Lymphocyte; Genetics; Complication; Lupus erythematosus; BXSB mice; Kidney disease; Immunopathology; Connective tissue disease; Urinary system disease; Rodentia; MRL mice; Genotype; Myeloid cell; Pathology; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1999.00847.x

Both MRL‐lpr/lpr (lpr) and BXSB mice fall victim to autoimmune disease as a function of age. To combine their properties, brother–sister mating of (female lpr × male BXSB)F1 mice was done. Mice for mating were selected according to indicators of early onset of glomerulonephritis and subsequent early death (i.e., EOD). This mating was continued for more than 16 generations. The EOD mice thus established had homozygous H‐2k/k, lpr/lpr, and possible yaa/‐ (in the case of males). The average life span of males was 83 days while that of females was 126 days. After 12 weeks of age, the majority (> 80%) of male EOD mice were characterized by the abnormality of urine due to glomerulonephritis. We then characterized how glomerulonephritis was evoked, especially in terms of expanding lymphocyte subsets in various immune organs. Similar to the case of parental lpr mice, the major expanding cells were CD4−8−B220+ TCRint cells in the immune organs and kidney. In addition, myeloid cells were found to infiltrate the kidney. This massive infiltration of both TCRint cells and myeloid cells might be responsible for the onset of acute glomerulonephritis. Even after more than 50 generations, these EOD mice still carry both lpr and yaa genes. These results suggest that EOD mice might be a very useful tool for the study of acute lupus glomerulonephritis which is evoked by the genetic abnormalities.