Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  1
• Reference
  J:204320 Cao Y, et al., Congenic mice provide evidence for a genetic locus that modulates spontaneous arthritis caused by deficiency of IL-1RA. PLoS One. 2013;8(6):e68158
• ID
  MGI:5827926

Genes

Gene	Assay Type
Liq1	visible phenotype

Notes

• Experiment
  To confirm the importance of QTL Liq1 (limb inflammation QTL 1) in the development of spontaneous arthritis, and to identify potential candidate genes, 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.
  
  Genetic markers were used to assist in the selection of progeny in each generation to backcross to the CA.129-Il1rn^tm1Yiw (BALB/c-/-) mice. By the 6th generation all of the chromosomes in the progeny were BALB/c in origin with the exception of portions of Chr 1. Next, selected mice were intercrossed to produce homozygous strains containing the genomic BALB/c-/- background except for the QTL region on Chr 1 that was from D1.129(CA)-Il1rn^tm1Yiw (DBA/1-/-).
  
  Two congenic strains were created with overlapping homozygous DBA/1 DNA segments:
  CA.Cg-(D1Mit55-D1Mit209)^DBA/1 Il1rn^tm1Yiw (BALB.D1-1-/-); and
  CA.Cg-(D1Mit359-Tel)^DBA/1 Il1rn^tm1Yiw (BALB.D1-2-/-)
  
  The two new strains were observed for the development of spontaneous arthritis. Individual mice were visually inspected for the presence of arthritis: limb swelling, redness and swelling of joint and ankle, severe swelling and burned out and deformed limbs. The disease severity of a mouse was calculated with total scores of all limbs divided by the maximal score possible. The disease severity of a strain was calculated with the total scores of all mice divided by the total number of mice. The incidence was calculated with the number of affected mice divided by the total number of mice.
  
  Both congenic strains were relatively resistant to spontaneous arthritis and had delayed onset and reduced severity of the disease. The data appeared to confirm significant protection from spontaneous arthritis conferred by the DNA from the DBA/1 mice. However, the protection was only partial since the incidence of spontaneous arthritis ultimately approached 100% in each of the strains tested.
  
  The genes that regulate 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. [Fig 1.]
  Within this 23.73 Mb genomic region 115 genes were identified as relevant to arthritis and its potential pathways. [Table S2.] Six genes: Fcgr3, Capn2, Dedd, Fcer1g, Tfb2m and Ifi202 are co-expressed with Il1rn and related genes. Four genes are differentially expressed between CA.129-Il1rn^tm1Yiw and D1.129(CA)-Il1rn^tm1Yiw: Fcer1g, Fcgr3, Ifi202b and Kmo. The same region is syntenic to human Chr 1 in two regions, 1:165171104 bp - 158516918 bp and 1:240177648 bp - 209788220 bp.