Publication: Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL-MpJ
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Date
2008
Authors
Ichii, Osamu ; Konno, Akihiro ; Sasaki, Nobuya ; Endoh, Daiji ; Hashimoto, Yoshiharu ; Kon, Yasuhiro
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
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-
100cM) 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.
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