A non-major histocompatibility locus determines tissue specificity in the pathogenic process underlying synovial proliferation in a mouse arthropathy model.
BACKGROUND
The incidence and characteristics of spontaneous ankylosis in the ankle of specific F(1) mice descended from two Fas-deficient strains were reported. Here the coincidence of synovial proliferation and ankylosis in the descendent F(2) mice is reported.


OBJECTIVE
To clarify whether the two distinct manifestations are genetically different.


METHODS
An arthropathic group of mice (MCF(2)) were bred by intercrossing MRL/Mp.Fas(lpr)-sap(-)/sap(-) and C3H/He.Fas(lpr) mice. All mice were killed by bleeding under anaesthesia when they were 6 months old. Pathological grades for synovial proliferation were determined by microscopical examination. To obtain a linkage locus, the whole genome of male MCF(2) mice was scanned by using 73 microsatellite markers.


RESULTS
Synovial proliferation was equally observed in male and female MCF(2) mice. No correlation was observed between the grades of synovial proliferation and the ankylosis occurring in the MCF(2) mice. A suggestive susceptibility locus was shown in the middle of chromosome 11. This locus was an MRL allele with a recessive inheritance mode.


CONCLUSIONS
The pathogenic mechanisms of synovial proliferation and ankylosis are genetically different. The present locus is overlapped with some loci associated with rheumatoid arthritis and with others associated with experimental arthritides.
Zhang
Ming-Cai
MC
Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
Mori
Shiro
S
Date
Fumiko
F
Furukawa
Hiroshi
H
Ono
Masao
M
D000818:Animals; D001947:Breeding; D049109:Cell Proliferation; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006651:Histocytochemistry; D007592:Joint Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D018895:Microsatellite Repeats; D012216:Rheumatic Diseases / Q000235:genetics* / Q000473:pathology; D013583:Synovial Membrane / Q000473:pathology*