Studies of congenic lines in the Brown Norway rat model of Th2-mediated immunopathological disorders show that the aurothiopropanol sulfonate-induced immunological disorder (Aiid3) locus on chromosome 9 plays a major role compared to Aiid2 on chromosome 10.
Brown Norway (BN) rats treated with aurothiopropanol-sulfonate (Atps) constitute a model of Th2-mediated immunological disorders associated with elevated IgE responses and renal IgG deposits. Using F(2) offspring between Atps-susceptible BN and Atps-resistant Lewis rats, we had previously mapped three quantitative trait loci on chromosomes 9, 10, and 20 for which BN alleles increased susceptibility to Atps-induced immunological disorders (Aiid). In this study we have used congenic lines for the latter two quantitative trait loci, formerly called Atps2 and Atps3 and now named Aiid2 (chromosome 10) and Aiid3 (chromosome 9), for fine mapping and characterization of their impact on Atps-triggered reactions. In Aiid2 congenic lines, the gene(s) controlling part of the IgE response to Atps was mapped to an approximately 7-cM region, which includes the IL-4 cytokine gene cluster. Two congenic lines in which the introgressed segments shared only a portion of this 7-cM region, showed an intermediate IgE response, indicating the involvement of several genes within this region. Results from BN rats congenic for the Lewis Aiid3 locus, which we mapped to a 1.2-cM interval, showed a stronger effect of this region. In this congenic line, the Atps-triggered IgE response was 10-fold lower than in the BN parental strain, and glomerular IgG deposits were either absent or dramatically reduced. Further genetic and functional dissections of these loci should provide insights into pathways that lead to Th2-adverse reactions.
Mas
Magali
M
Centre de Physiopathologie de Toulouse Purpan, Département Génétique Fonctionnelle des Maladies des Epithéliums, Institut National de la Santé et de la Recherche Médicale, Unité 563, Hôpital Purpan and Université Paul Sabatier, Toulouse, France.
Cavaillès
Pierre
P
Colacios
Céline
C
Subra
Jean-François
JF
Lagrange
Dominique
D
Calise
Maryline
M
Christen
Marie-Odile
MO
Druet
Philippe
P
Pelletier
Lucette
L
Gauguier
Dominique
D
Fournié
Gilbert J
GJ
D000818:Animals; D020296:Animals, Congenic; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004112:Dimercaprol / Q000009:adverse effects* / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D006046:Gold / Q000009:adverse effects*; D007154:Immune System Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000009:adverse effects*; D010641:Phenotype; D020005:Propanols; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013438:Sulfhydryl Compounds; D018418:Th2 Cells / Q000276:immunology*
D005819:Genetic Markers; D007074:Immunoglobulin G; D050607:Organogold Compounds; D009942:Organometallic Compounds; D020005:Propanols; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D007073:Immunoglobulin E; D006046:Gold; C013394:aurotioprol