The production of two Th2 cytokines, interleukin-4 and interleukin-10, is controlled independently by locus Cypr1 and by loci Cypr2 and Cypr3, respectively.
The strains BALB/cHeA (BALB/c) and STS/A (STS) differ in production of IL-4 and IL-10, two Th2 cytokines, after stimulation of spleen cells with Concanavalin A, STS being a low and BALB/c a high producer. We analyzed the genetic basis of this strain difference using the recombinant congenic (RC) strains of the BALB/c-c-STS/Dem (CcS/Dem) series. This series comprises 20 homozygous strains. Each CcS/Dem strain contains a different, random set of approximately 12. 5% genes of the "donor" strain STS and approximately 87.5% of the "background" strain BALB/c. We selected for further analysis the RC strain production intermediate between BALB/c and STS. In (CcS-20xBALB/c)F2 hybrids we found that different loci control expression of IL-4 and IL-10. Cypr1 (cytokine production 1) on chromosome 16 near D16Mit15 controls IL-4 production, whereas the production of IL-10 is influenced by loci Cypr2 near D1Mit14 and D1Mit227 on chromosome 1 and Cypr3 marked by D5Mit20 on chromosome 5. In addition, the relationship between the level of these two cytokines depends on the genotype of the F2 hybrids at a locus cora1 (correlation 1) on chromosome 5. This differential genetic regulation may be relevant for the understanding of biological effects of T-helper cells in mice of different genotypes.
Kosarová
M
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Praha.
Havelková
H
H
Krulová
M
M
Demant
P
P
Lipoldová
M
M
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D008040:Genetic Linkage / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology; D005838:Genotype; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000378:metabolism*
D005819:Genetic Markers; D016753:Interleukin-10; D015847:Interleukin-4