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Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA

Authors
  • Deng, Nan1
  • Jiao, Yan2, 3
  • Cao, Yanhong2, 4
  • Liu, Xiaoyun2
  • Ma, Yonghui2
  • Hasty, Karen A1, 2, 5
  • Brand, David D1, 5, 6
  • Stuart, John M1, 5
  • Gu, Weikuan2, 5
  • 1 University of Tennessee Health Science Center, Department of Medicine, Memphis, TN, 38163, USA , Memphis (United States)
  • 2 University of Tennessee Health Science Center, Departments of Orthopaedic Surgery and Biomedical Engineering, Memphis, TN, 38163, USA , Memphis (United States)
  • 3 Mudanjiang Medical College, Heilongjiang, Mudanjiang, 157001, PR China , Mudanjiang (China)
  • 4 Harbin Medical University, Institute of Kaschin-Beck Disease, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Laboratory of Etiologic Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618104), Harbin, 150081, China , Harbin (China)
  • 5 Veterans Affairs Medical Center, Research Service, 1030 Jefferson Avenue, Memphis, TN, 38104, USA , Memphis (United States)
  • 6 University of Tennessee Health Science Center, Department of Microbiology, Immunology and Biochemistry, Memphis, TN, 38163, USA , Memphis (United States)
Type
Published Article
Journal
BMC Immunology
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 09, 2014
Volume
15
Issue
1
Identifiers
DOI: 10.1186/s12865-014-0057-9
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundTo 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.ConclusionThe 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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