Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  1
• Reference
  J:237436 Deng N, et al., Genomic locus on chromosome 1 regulates susceptibility to spontaneous arthritis in mice deficiency of IL-1RA. BMC Immunol. 2014 Dec 09;15:57
• ID
  MGI:6101507

Genes

Gene	Assay Type
Liq1	visible phenotype

Notes

• Experiment
  Previously QTL mapping was used to identify the genetic factors that regulate spontaneous arthritis. Susceptible, IL-1ra deficient BALB/c mice, CA.129-Il1rn^tm1Yiw, were crossed with resistant DBA/1 IL-1ra-deficient mice, D1.129(CA)-Il1rn^tm1Yiw, to generate F1 mice which were then crossed to produce F2 mice. QTL Liq1 ( (limb inflammation 1) was identified on the distal end of Chromosome 1 in that study [J:239222].
  
  In a followup study [J:204320] speed congenics were generated to transfer the Liq1 QTL region from resistant IL-1ra deficient DBA/1 mice to susceptible IL-1ra deficient BALB/c mice. Two congenic strains were created with overlapping homozygous DBA/1 DNA segments:
  CAJcl.Cg-(D1Mit55-D1Mit209)^DBA/1Il1rn^tm1Yiw) (BALB.D1-1^-/-); and
  CAJcl.Cg-(D1Mit359-Tel)^DBA/1Il1rn^tm1Yiw ) (BALB.D1-2^-/-).
  The genes regulating QTL Liq1 appeared to be located in the region of the QTL that was shared by both congenic strains, between D1Mit110 and D1Mit209 on Chromosome 1.
  
  In the current study the Liq1 genomic fragment from Chromosome 1 of BALB/c^-/- (CA.129-Il1rn^tm1Yiw) was transferred onto the DBA/1^-/- (D1.129(CA)-Il1rn^tm1Yiw) genomic background to investigate the effect of the DBA/1 genomic background on the function of genes within the Liq1 locus. A new congenic strain D1.BALB-1 (D1.Cg-(D1Mit506-Tel)^BALB/cIl1rn^tm1Yiw ) was created and observed for the development of spontaneous arthritis.
  
  Disease expression in 14 mice from each of the new congenic line and from the DBA/1 mice were recorded respectively. Compared to the 14 mice from DBA/1, the congenic strain had significantly increased severity and incidence of spontaneous arthritis (P value=5.33637E-10 and 9.68472E-12, respectively). These findings indicated that the QTL fragment on Chr 1, for susceptibility to spontaneous arthritis, worked in both directions.
  
  By comparing the genetic markers in the three congenic strains (the two from J:204320 and the new one generated here in the current study) the region of interest could be reduced to a final common transferred region. The estimated size of the transferred regions in the DBA.B1-1 was from D1Mit506 to the distal end. Previously, the two congenic strains of BALB/c background mapped between D1Mit55 and D1Mit209 in BALB.D1-1 and between D1Mit359 and the distal end in BALB.D1-2 (Figure 1). The new data from DBA.B1-1 confirmed the previous estimation of the genomic size of the QTL region: The minimum size of the transferred genome region is between D1Mit359 and D1Mit209. The maximum size is between D1Mitt110 and the distal end.
  
  Splenocytes and lymphocytes from each strain were cultured with anti-CD3/ CD28 expansion beads for 48 hours, and cytokine levels were measured by Milliplex kit. The susceptible parental strain, BALB/c^-/- (CA.129-Il1rn^tm1Yiw), had the highest levels of four cytokines, Il-6, Tnf-alpha, Ifn-gamma and Il-17 while the resistant parental strain, DBA/1^-/-, (D1.129(CA)-Il1rn^tm1Yiw), had the lowest levels of these cytokines. The levels of these cytokines in congenic strains were in between the two parental strains. Particularly, the expression level of Il-17 in the spleen of congenic DBA/1^-/- mice was at levels 10-fold greater than that in the DBA/1^-/- arthritis resistant strain.