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Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA
BACKGROUND: 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 spontaneou...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272550/ https://www.ncbi.nlm.nih.gov/pubmed/25488730 http://dx.doi.org/10.1186/s12865-014-0057-9 |
Sumario: | BACKGROUND: 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. RESULT: Instead of BALB/c(−/−), DBA/1(−/−) was used as the recurrent parent while BALB/c(−/−) was used as the donor parent. By the 6(th) 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. |
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