Experiment
QTL associated with the modification of experimental allergic encephalomyelitis (EAE) due to non-genetic factors, such as age and time of season, were mapped in 760 (B10.S/DvTe x SJL/J)F2 intercross animals using 170 microsatellite markers (average spacing = 10 cM) in the genome scan. Animals were immunized with mouse spinal cord homogenate at an average age of 15.3 +/- 10.5 weeks of age. Animals were monitored for symptoms of EAE from 10 to 60 days post-immunization.
Linkage to EAE susceptibility in 6- to 12-week old animals and summer cohorts coincided with previously identified QTL Eae43 at 50 cM (62.26 Mb; D7Mit233) on mouse Chromosome 7 and Eae5 at 21.1 cM (38.72 Mb; D17Mit105) on mouse Chromosome 17. Eae11 at 41 cM (69.73 Mb; D16Mit140) on mouse Chromosome 16 was also detected in this cohort.
When a summer cohort of 366 F2 animals at an average age of 31 +/- 12 weeks was analyzed, significant linkage to EAE susceptibility was detected at a novel locus on mouse Chromosome 4 near D4Mit221 (58 cM),D4Mit203 (60 cM), and D4Mit204 (61.9 cM). This locus is named Eae40 (author's designation is Eae36). Eae40 maps near several previously identified autoimmune loci, such as Lbw2 (42.6 cM), Lbm1 (26.3 cM), Arvm2 (58 cM), Sles2 (58 cM), Idd9.1 (60 cM), and Idd11 (64.6 cM). Potential candidate genes identified near the Eae40 interval are Csf3r (57.5 cM), Pnrc2 (66.7 cM), and Htr1d (66 cM). Amino acid substitutions are present in Pnrc2 (L41H) and Htr1d (A22V) protein sequences between inbred strains SJL/J andC57BL/10.
Analysis Tools