Genetic Selection for Crescent Formation Yields Mouse Strain with Rapidly Progressive Glomerulonephritis and Small Vessel Vasculitis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 8; pp. 3413 - 3417
• Main Authors: Kinjoh, Koken, Kyogoku, Masahisa, Good, Robert A.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.04.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antibodies; Biological and medical sciences; Blood vessels; Chromosome Mapping; Coronary Circulation; Crosses, Genetic; Disease; Female; Fibrin - analysis; Glomerulonephritis; Glomerulonephritis - genetics; Glomerulonephritis - pathology; Glomerulonephritis - physiopathology; Immunity (Disease); Immunohistochemistry; Kidney - blood supply; Kidney - pathology; Kidneys; Lesions; Male; Medical sciences; Mice; Mice, Inbred Strains; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Ovary - blood supply; Proteinuria; Rodents; Selection, Genetic; Sex Factors; Species Specificity; Spleen; Spleen - blood supply; Stomach - blood supply; Systemic vasculitis; T lymphocytes; Vasculitis; Vasculitis - genetics; Vasculitis - pathology; Vasculitis - physiopathology; Glomerulonephritis; Animal model; Urinary system disease; Necrotizing vasculitis; Pathogenesis; Rodentia; Inheritance; Cardiovascular disease; Renal disease; Hereditary; Vascular disease; Pathology; Vertebrata; Mammalia; Mouse
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.8.3413

We have established a recombinant inbred strain of mouse named spontaneous crescentic glomerulonephritis-forming mouse/Kinjoh or SCG/Kj. Mice of this strain spontaneously develop rapidly progressive glomerulonephritis. This strain of mice was derived from (BXSB/Mp x MRL/Mp-lpr/lpr)F1hybrid mice by brother x sister mating coupled with repeated histopathologic selection for breeding of mice whose parents had the highest frequency of crescent formation in the kidneys. In this strain of mice, nephritis appears earlier and is more rapidly progressive than in any other murine model of systemic lupus erythematosus. Histopathologically, the characteristic renal lesions in the mice of this strain express a most dramatic form of crescentic glomerulonephritis. The lesions in the kidneys show only slight fine granular immune deposits along the glomerular basement membrane associated with remarkable extraglomerular proliferation and hemorrhage in Bowman's space. Although selection was not based on vasculitis, mice of this strain also exhibit a high incidence of necrotizing vasculitis. These vascular lesions involve primarily small arteries and arterioles and many organs and tissues but spare the kidneys. Thus this form of vasculitis has been found to be correlated with the crescentic form of glomerulonephritis but not with lymphoid hyperplasia of the spleen. We conclude that, in this strain of mouse, the rapidly progressive glomerulonephritis is genetically restricted and that this genetic restriction is firmly linked to that responsible for the vasculitis.