TY - JOUR
T1 - Arthritis in MRL/lpr mice is under the control of multiple gene loci with an allelic combination derived from the original inbred strains
AU - Kamogawa, Junji
AU - Terada, Miho
AU - Mizuki, Shinichi
AU - Nishihara, Miyuki
AU - Yamamoto, Haruyasu
AU - Mori, Shiro
AU - Abe, Yoriko
AU - Morimoto, Koji
AU - Nakatsuru, Syuichi
AU - Nakamura, Yusuke
AU - Nose, Masato
PY - 2002
Y1 - 2002
N2 - Objective. To clarify the mode of inheritance and the genome origins of arthritis in a lupus-prone strain of mice, MRL/MpJ, bearing a Fas deletion mutant gene, lpr (MRL/lpr). Methods. Using non-lupus-prone strains of mice, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/Ipr × C3H/Ipr)F1 intercross and MRL/lpr × (MRL/lpr × C3H/lpr)F1 back-cross mice were prepared. Arthritis in individual mice was analyzed by histopathologic grading, and the genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis to determine the polymorphic microsatellite markers highly associated with arthritis. Results. Arthritis-susceptibility loci with significant linkage were mapped between D15Mit111 and D15Mit18 (map position 17.8-18.7 cM) on chromosome 15 and between D19Mit112 and D19Mit72 (map position 43.0-55.0) on chromosome 19 (logarithm of odds scores 3.5 and 4.3, respectively). Three other loci, one mapped to each of chromosomes 1, 2, and 7, showed suggestive linkage. Loci homozygous for MRL alleles on chromosomes 1 and 19 enhanced arthritis in both sexes, whereas other loci on chromosomes 2 and 15 selectively affected males. A locus homozygous for MRL alleles on chromosome 7 inhibited arthritis in both sexes. Three of these loci were found to originate from an LG/J strain and 1 from an AKR/J strain. Some combinations of these loci showed an additive effect in a hierarchical manner on the development of arthritis. Conclusion. Arthritis in MRL/lpr mice is a complex pathologic manifestation resulting from the cumulative effect of multiple gene loci with an allelic combination derived from the original inbred strains.
AB - Objective. To clarify the mode of inheritance and the genome origins of arthritis in a lupus-prone strain of mice, MRL/MpJ, bearing a Fas deletion mutant gene, lpr (MRL/lpr). Methods. Using non-lupus-prone strains of mice, C3H/HeJ-lpr/lpr (C3H/lpr), (MRL/Ipr × C3H/Ipr)F1 intercross and MRL/lpr × (MRL/lpr × C3H/lpr)F1 back-cross mice were prepared. Arthritis in individual mice was analyzed by histopathologic grading, and the genomic DNA of the backcross mice was examined by simple sequence-length polymorphism analysis to determine the polymorphic microsatellite markers highly associated with arthritis. Results. Arthritis-susceptibility loci with significant linkage were mapped between D15Mit111 and D15Mit18 (map position 17.8-18.7 cM) on chromosome 15 and between D19Mit112 and D19Mit72 (map position 43.0-55.0) on chromosome 19 (logarithm of odds scores 3.5 and 4.3, respectively). Three other loci, one mapped to each of chromosomes 1, 2, and 7, showed suggestive linkage. Loci homozygous for MRL alleles on chromosomes 1 and 19 enhanced arthritis in both sexes, whereas other loci on chromosomes 2 and 15 selectively affected males. A locus homozygous for MRL alleles on chromosome 7 inhibited arthritis in both sexes. Three of these loci were found to originate from an LG/J strain and 1 from an AKR/J strain. Some combinations of these loci showed an additive effect in a hierarchical manner on the development of arthritis. Conclusion. Arthritis in MRL/lpr mice is a complex pathologic manifestation resulting from the cumulative effect of multiple gene loci with an allelic combination derived from the original inbred strains.
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U2 - 10.1002/art.10193
DO - 10.1002/art.10193
M3 - Article
C2 - 11953986
AN - SCOPUS:0036226155
SN - 0004-3591
VL - 46
SP - 1067
EP - 1074
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 4
ER -