Rat chromosome 9 bears a major susceptibility locus for IgE response.
Injection of Brown Norway (BN) rats with gold salts provides a model to analyze the genetic control of the IgE response. A cohort of F2 progeny of susceptible BN and resistant LEW strains has been studied to carry out a genome-wide search for loci controlling the IgE response. Genome scanning identified two previously described loci, Atps1 and Atps2, and a new locus, Atps3. Atps1 linked to the MHC and Atps2 linked to the cytokine gene cluster that included the IL-4 region have been previously associated with serum IgE concentrations and with other Th2-dependent immune manifestations triggered by gold salts. The new interval, Atps3, identified on chromosome 9 (Lod score = 16), appears to play a major role in the control of the IgE response since it accounts for 31% of the genetic variance. Moreover, Atps3 is linked to anti-laminin antibody response and to glomerular immunoglobulin deposits. The identification and functional characterization of genes involved in these regions, particularly in Atps3, may shed light on the pathogenesis of atopic diseases in man.
Mas
M
M
Institut National de la Santé et de la Recherche Médicale U28, Hôpital Purpan and Université Paul Sabatier, Toulouse, France.
Subra
J F
JF
Lagrange
D
D
Pilipenko-Appolinaire
S
S
Kermarrec
N
N
Gauguier
D
D
Druet
P
P
Fournié
G J
GJ
D000818:Animals; D002874:Chromosome Mapping; D004112:Dimercaprol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000494:pharmacology*; D020005:Propanols; D019655:Quantitative Trait, Heritable; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013438:Sulfhydryl Compounds
D050607:Organogold Compounds; D009942:Organometallic Compounds; D020005:Propanols; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D007073:Immunoglobulin E; C013394:aurotioprol