Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  15
• Reference
  J:137478 Glant TT, et al., Two loci on chromosome 15 control experimentally induced arthritis through the differential regulation of IL-6 and lymphocyte proliferation. J Immunol. 2008 Jul 15;181(2):1307-14
• ID
  MGI:3803901

Genes

Gene	Assay Type
Pgia8	resistance/susceptibility
D15Mit12	PCR amplified length variant
D15Mit267	PCR amplified length variant
Pgia9	resistance/susceptibility
D15Mit41	PCR amplified length variant

Notes

• Experiment
  Previously identified arthritis susceptibility QTLs Pgia8 (proteoglycan induced arthritis 8) and Pgia9 (proteoglycan induced arthritis 9) on mouse Chromosome 15 were further characterized in this study using congenic line analysis. Progenitor strain DBA/2 is resistant to proteoglycan induced arthritis whereas BALB/c is susceptible. Starting at 12 weeks of age, congenic animals were injected with PG protein over a period of 63 days in 2-week intervals and assessed for arthritis severity.
  
  Pgia8 is locatedon the proximal portion of chromosome 15. A congenic line carrying a DBA/2-derived DNA segment encompassing Pgia8 from D15Mit12 (4.7 cM) to D15Mit267 (10.9 cM) on a BALB/c genetic background was constructed. This locus appears to have a suppressive effecton PGIA in female congenic animals. Pgia8 is located near several previously identified autoimmunity and arthritis QTLs such as Cia30 (9.9 cM), Cia31 (9.6 cM), Cia32 (17.8 cM), Eae2 (15.5 cM), Paam1 (18 cM), Bbaa14 (17 cM) and Mbis3 (17 cM). Pgia8 also appears to interact with Pgia26 on mouse Chromosome 3 at 52.5 cM.
  
  Pgia9 is located on the distal portion of chromosome 15. A congenic line was constructed which carries DBA/2-derived DNA from D15Mit267 (10.9 cM) to D15Mit41(54.5 cM) on a BALB/c genetic background. Pgia9 displayed a strong PGIA resistant effect in both male and female animals with delayed disease onset by at least 2 weeks. The incidence of PGIA was decreased approximately 50% in females. Male congenics also displayed approximately 10% reduced PGIA incidence but with lower statistical significance. Ncf4 at 47.2 cM is a potential candidate gene for Pgia9. Several QTLs are located near Pgia9 including Eae32 (32 cM), Eae38 (55 cM) and Bbaa22 (46.9 cM). Rat QTL Pia17 (pristine induced arthritis17) is located in a region of rat chromosome 7 orthologous to Pgia9.
  
  Chromosome 15 loci involved in IL-6 production and PGIA susceptibility were also mapped using 195 (BALB/c x BALB/c-Chr15^DBA/2)F2 intercross animals. Linkage to IL-6 production and PGIA score mapped to regions of chromosome 15 overlapping with Pgia8 and Pgia9, thus confirming the QTLs. It was observed that Pgia8 is linked to arthritis susceptibility in females and IL-6 production in males while Pgia9 is linked to arthritis susceptibility and IL-6 production in both genders. DBA/2-derived alleles at Pgia8 decreased IL-6 production 3-fold in females while DBA/2-derived alleles at Pgia9 increased IL-6 production 2-fold in both sexes.
  
  TNF-alpha production during PGIA disease also showed linkage to Pgia8 and Pgia9. DBA/2-derived alleles at Pgia8 and Pgia9 increased TNF-alpha production by 1.5- to 2-fold.