Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ.
In lupus erythematosus-prone mice, including the BXSB, NZW and NZB strains, telomeric regions of chromosome 1 (Chr.1) contain major glomerulonephritis susceptibility loci such as Bxs3, Sle1, and Nba2. To assess whether strain MRL, a model for lupus erythematosus, had glomerulonephritis susceptibility loci on Chr.1, we created B6.MRLc1(82-100) congenic mice carrying MRL/MpJ Chr.1 (82-100 cM) based on the C57BL/6 background and investigated renal pathology. From 6 months of age, B6.MRLc1 (82-100) showed the onset of diseases such as splenomegaly due to proliferation of CD3- or B220-positive cells, glomerular damage, and an increased serum anti-dsDNA antibody concentration, and these were earlier and severer in females. The score for glomerular damage was higher in B6.MRLc1(82-100) mice over 12 months old than in C57BL/6 or even in wild-type MRL/MpJ. Immune-complex depositions were demonstrated on glomerular basement membrane in B6.MRLc1(82-100) by immunohistochemistry and electron microscopy. For the percentage of IgG1-positive glomeruli, B6.MRLc1 (82-100) had significantly higher values than C57BL/6. In evaluations of clinical parameters, serum levels of blood urea nitrogen and the anti-dsDNA antibody in B6.MRLc1(82-100) were significantly higher than those in C57BL/6. In conclusion, B6.MRLc1(82-100) clearly developed autoimmune-mediated glomerulonephritis, and we demonstrated that MRL Chr.1 contained a novel glomerulonephritis susceptibility locus. We named this locus Mag (MRL autoimmune glomerulonephritis) and it provided new insights into the genetic basis and pathogenesis of lupus nephritis.
Ichii
O
O
Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Konno
A
A
Sasaki
N
N
Endoh
D
D
Hashimoto
Y
Y
Kon
Y
Y
D000375:Aging / Q000502:physiology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015551:Autoimmunity; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005921:Glomerulonephritis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018895:Microsatellite Repeats; D020161:Physical Chromosome Mapping; D012720:Severity of Illness Index; D012737:Sex Factors; D016615:Telomere / Q000235:genetics*
D001323:Autoantibodies; D005819:Genetic Markers; D007074:Immunoglobulin G