Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes.
BACKGROUND
In a cross between two mouse strains, the susceptible B10.RIII (H-2(r)) and resistant RIIIS/J (H-2(r)) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease indifferent experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA).


METHODS
CIA, induced by immunisation with bovine type II collagen, was studied in Eae39 congenic and sub-interval congenic mice. Antibody titres were investigated with ELISA.Gene-typing was performed by micro-satellite mapping and statistics was calculated by standard methods.


RESULTS
Experiments of CIA in Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titres. Two of the loci promoted disease and the third locus was protected against CIA development. By further breeding of mice with small congenic fragments, we identified a 3.2 mega base pair (Mbp)interval that regulates disease.


CONCLUSIONS
Disease-promoting and disease-protecting genes within the Eae39 locus on mouse chromosome 5 control susceptibility to CIA. A disease-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases.
Department of Experimental Medical Science, Unit for Medical Inflammation Research, BMC l11, Lund Unviersity, S-221 84 Lund, Sweden.
Therese
T
Lindvall
Jenny
J
Karlsson
Rikard
R
Holmdahl
Asa
A
Andersson
D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000235:genetics*; D002417:Cattle; D002875:Chromosomes / Q000235:genetics*; D024043:Collagen Type II / Q000008:administration & dosage* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics
D024043:Collagen Type II