title: Chromosomal mapping of hyperserum IgA and glomerular IgA deposition in a high IgA (HIGA) strain of DdY mice.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nogaki
authors.forename: Emi
authors.initials: E
authors.lastname: Oida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kamata
authors.forename: Ikei
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Nomura
authors.forename: Katsuo
authors.initials: K
authors.lastname: Suyama
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tahara
authors.forename: Takahiko
authors.initials: T
authors.lastname: Ono
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Eri
authors.initials: E
authors.lastname: Muso
mesh_terms: 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
chemical_list: D007070:Immunoglobulin A