title: Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. ndeng@uthsc.edu.
authors.forename: Nan
authors.initials: N
authors.lastname: Deng
authors.affiliation: Departments of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. yjiao2@uthsc.edu.|Mudanjiang Medical College, Mudanjiang, Heilongjiang, 157001, PR China. yjiao2@uthsc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Departments of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. audreycao@yahoo.com.|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 Medical University, Harbin, 150081, China. audreycao@yahoo.com.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Departments of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. liuxyun6@mail2.sysu.edu.cn.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. yong201101@yahoo.com.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. khasty@uthsc.edu.|Departments of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. khasty@uthsc.edu.|Research Service, Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. khasty@uthsc.edu.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Hasty
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. dbrand@uthsc.edu.|Research Service, Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. dbrand@uthsc.edu.|Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. dbrand@uthsc.edu.
authors.forename: David D
authors.initials: DD
authors.lastname: Brand
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. jstuart@uthsc.edu.|Research Service, Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. jstuart@uthsc.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Stuart
authors.affiliation: Departments of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. wgu@uthsc.edu.|Research Service, Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA. wgu@uthsc.edu.
authors.forename: Weikuan
authors.initials: W
authors.lastname: Gu
mesh_terms: D000818:Animals; D001168:Arthritis / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D040641:Quantitative Trait Loci