Quantitative trait loci (QTL) analysis reveals a close linkage between the hinge region and trimeric IgA dominancy in a high IgA strain (HIGA) of ddY mice.
Polymerization of IgA has been suggested as one of the causes of mesangial deposition in IgA nephropathy. HIGA mice are an inbred model of IgA nephropathy, established by selective mating of ddY mice. This strain is characterized by a unique profile of the IgA molecule that is dominantly polymeric and has high serum levels with intense IgA deposition on the mesangium. We carried out quantitative trait loci (QTL) analysis, using F2 generations by crossing HIGA with BALB/c mice. Significant linkage of polymeric IgA in serum samples was identified around D12Mit263, which is close to the gene of the immunoglobulin heavy chain on chromosome 12. The amino acid sequence of the alpha heavy chain revealed marked differences between BALB/c and HIGA mice. Furthermore, most differences were focussed on the hinge region. The DBA/2J strain, which has the same amino acid sequence in the hinge region as the HIGA strain, also showed polymeric IgA dominance but low IgA levels in sera. Size fraction analysis revealed that these polymeric IgA showed trimer dominance in both DBA/2J and HIGA mice. In conclusion, the hinge region plays a key role in trimeric IgA formation in HIGA mice.
Oida
Emi
E
Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan.
Nogaki
Fumiaki
F
Kobayashi
Ikei
I
Kamata
Tadashi
T
Ono
Takahiko
T
Miyawaki
Shigeki
S
Serikawa
Tadao
T
Yoshida
Haruyoshi
H
Kita
Toru
T
Muso
Eri
E
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D008040:Genetic Linkage; D007070:Immunoglobulin A / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D040641:Quantitative Trait Loci
D007070:Immunoglobulin A