Eae39r QTL Detail

Summary

• Symbol
  Eae39r
• Name
  Eae39 region resistant to collagen induced arthritis

• Feature Type
  QTL
• IDs
  MGI:4410559
• Candidate Genes
  1 Gene

Location &
Maps

• Sequence Map
  Genome coordinates not available from the current reference assembly.

• Genetic Map
  Chromosome 5, cM position of peak correlated region/marker: Syntenic
• Mapping Data
  2 experiments

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  2 phenotype references
  

• All Mutations and Alleles
  2
• QTL
  2
• Find Mice (IMSR)
  0 strains or lines available

References

• Summaries
  All 2

  Phenotypes 2
• Earliest
  J:153378 Lindvall T, et al., Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes. Arthritis Res Ther. 2009 Jan 20;11(1):R10
• Latest
  J:295093 Sardar S, et al., The oncoprotein TBX3 is controlling severity in experimental arthritis. Arthritis Res Ther. 2019 Jan 10;21(1):16

Candidate Genes for Eae39r:

Gene	Genome Location (GRCm39)	Reference	QTL Note
Tbx3	Chr5:119808734-119822789 (+)	J:295093	Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease and in experimental models for disease. The genetic locus Eae39, located on mouse chromosome 5, was previously linked to experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis. Subsequently, it was also shown to influence CIA development and severity [8, 10]. Eae39 congenic and sub-congenic lines were bred on the genetic background of the B10.RIII strain [7]. In the present study, the Eae39 sub-locus, Eae39r, was investigated. This locus comprises four protein-coding genes: Mediator complex subunit 13-like (Med13l), T-box transcription factor 3 (Tbx3), T-box transcription factor 5 (Tbx5), and Probable RNA-binding protein 19 (Rbm19). The authors previously showed that genetic polymorphisms in Med13L do not affect the immune phenotype in BR.RIIIS/J-Eae39r congenic mice and are predicted to be non-disease associated (Sardar et al., 2018). BR.RIIIS/J-Eae39r congenic mice were produced by introduction of the Eae39r fragment from the CIA-resistant RIIIS/J donor strain, purchased from Jackson Laboratory (Bar Harbor, ME, USA), to the CIA susceptible B10.RIII background strain, provided by J. Klein (Tbingen, Germany), as previously described [8]. The sub-congenic line BR.RIIIS/J-Eae39r2 was produced by further inter-crossing heterozygous BR.RIIIS/J-Eae39r mice. Purified genomic DNA was used for genotyping by high-resolution melting (HRM) SNP genotyping for rs33583463 (5:118596773 bp; mouse genome assembly GRCm38) and rs29824716 (5:120043597 bp; mouse genome assembly GRCm38). Gene expression studies have revealed differential expression of Tbx3 in B cells, where low expression was accompanied by a higher B cell response upon B cell receptor stimulation in vitro. Furthermore, we showed that serum TBX3 levels rise concomitantly with increasing severity of CIA. From these results, the authors suggest that TBX3 is a novel factor important for the regulation of gene transcription in the immune system and that genetic polymorphisms, resulting in lower expression of Tbx3, are contributing to a more severe form of CIA and high titers of autoantibodies. They also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.