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Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA
AllergologiaBackground:To understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1?/? mice that are resistant to spontaneous arthritis into BALB/c?/? mice which are susceptible. We were able to establish two congenic strains which exhibited a delayed onset and reduced severity of disease. In this study, we asked a different set of questions. How will the QTL region from BALB/c?/? interact with the rest of the genome in the DBA/1?/? background? Will the DBA/1?/? mice become susceptible to spontaneous arthritis if the QTL genomic region on chromosome 1 was replaced with the genomic fragment of the same region from BALB/c?/?? We conducted the congenic breeding with the similar procedure as that of congenic strains with BALB/c?/? background.ResultInstead of BALB/c?/?, DBA/1?/? was used as the recurrent parent while BALB/c?/? was used as the donor parent. By the 6th generation we determined that all of the chromosomes in the progeny were of DBA/1?/? origin with the exception of the QTL portion of chromosome 1 which is heterozygous of BALB/c?/? and DBA/1?/? origin. We then intercrossed selected mice to produce homozygous strains containing the homozygous genomic region of BALB/c?/? on chromosome 1, while the rest of genome are homozygous DBA/1?/?. This strain was observed for the development of spontaneous arthritis. Up to 9?weeks of age, both congenic strain and DBA/1?/? did not develop arthritis. However, after 9?weeks, the congenic strain started to exhibit signs of arthritis, while the DBA/1?/? remained free from disease.Conclusion:The result indicates a strong influence of genetic factor(s) on the QTL of chromosome 1 on the susceptibility to spontaneous arthritis. Identification of genetic factors within this QTL region in the future will significantly enhance our understanding of molecular mechanism of spontaneous arthritis.
Fonte: BMC Immunology

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