Chromosomal mapping of hyperserum IgA and glomerular IgA deposition in a high IgA (HIGA) strain of DdY mice.
BACKGROUND
The high IgA (HIGA) strain of ddY mice is an inbred model of IgA nephropathy (IgAN), established by selective mating of outbred ddY mice. HIGA mice show high levels of serum IgA and glomerulonephritis with mesangial IgA deposition. To identify the genetic loci responsible for hyperserum IgA and glomerular IgA deposition in this strain, quantitative trait loci analysis was carried out.


METHODS
By crossing HIGA with BALB/c mice, 244 F2 generations were produced. Serum IgA levels and glomerular IgA deposition were examined at 40 weeks of age. Genetic markers were typed at 105 microsatellites and the quantitative trait loci of hyperserum IgA and glomerular IgA deposition were confirmed using Map Manager QTX software.


RESULTS
Two significant quantitative trait loci of hyperserum IgA were identified on chromosome 2 [logarithm of odds (LOD) = 5.01] and chromsome 4 (LOD = 4.45), and a suggestive quantitative trait locus of hyperserum IgA was located on chromosome 1 (LOD = 3.49). On chromosome 15, a significant quantitative trait locus of glomerular IgA deposition was identified (LOD = 4.40) without the hyperserum IgA locus. Serum IgA level was weakly correlated with the intensity of glomerular IgA in 244 F2 mice; however, the quantitative trait loci of hyperserum IgA were not significantly associated with glomerular IgA deposition.


CONCLUSIONS
These findings indicate that, in HIGA mice, glomerular IgA deposition is mainly regulated by a quantitative trait locus on chromosome 15, and hyperserum IgA synergistically but weakly affect glomerular IgA deposition. The immune disturbance similar to IgAN was revealed to be under multigenic control in HIGA mice.
Nogaki
Fumiaki
F
Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan.
Oida
Emi
E
Kamata
Tadashi
T
Kobayashi
Ikei
I
Nomura
Keiko
K
Suyama
Katsuo
K
Tahara
Sachiko
S
Ono
Takahiko
T
Miyawaki
Shigeki
S
Serikawa
Tadao
T
Yoshida
Haruyoshi
H
Kita
Toru
T
Muso
Eri
E
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007070:Immunoglobulin A / Q000097:blood / Q000235:genetics*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats; D040641:Quantitative Trait Loci; D013045:Species Specificity
D007070:Immunoglobulin A