TY - JOUR
T1 - Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice
AU - Nakatsuru, Syuichi
AU - Terada, Miho
AU - Nishihara, Miyuki
AU - Kamogawa, Junji
AU - Miyazaki, Tatsuhiko
AU - Qu, Wei Min
AU - Morimoto, Koji
AU - Yazawa, Chie
AU - Ogasawara, Hideaki
AU - Abe, Yoriko
AU - Fukui, Keiko
AU - Ichien, Go
AU - Ito, Mitsuko R.
AU - Mori, Shiro
AU - Nakamura, Yusuke
AU - Nose, Masato
PY - 1999
Y1 - 1999
N2 - An MRL strain of mice bearing a Fas-deletion mutant gene, lpr, MRL/MpJ- lpr/lpr (MRL/lpr) develops collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjogren's syndrome, respectively. Development of such lesions seems dependent on host genetic background since the congenic C3H/HeJ-lpr/lpr (C3H/lpr) mice rarely develop them. To identify the gene loci affecting each lesion, a genetic dissection of these complex pathological manifestations was carried out. First, histopathological features in MRL/lpr, C3H/lpr, (MRL/lpr x C3H/lpr) F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice were analyzed. Genomic DNA of the backcross mice were subjected to association studies by Chi-squared analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. As a result, gene loci recessively associated with each lesion were mapped on different chromosomal positions. We concluded that each of these lesions in MRL/lpr mice is under the control of a different set of genes, suggesting that the complex pathological manifestations of collagen disease result from polygenic inheritance.
AB - An MRL strain of mice bearing a Fas-deletion mutant gene, lpr, MRL/MpJ- lpr/lpr (MRL/lpr) develops collagen disease involving vasculitis, glomerulonephritis, arthritis and sialoadenitis, each of which has been studied as a model for polyarteritis, lupus nephritis, rheumatoid arthritis and Sjogren's syndrome, respectively. Development of such lesions seems dependent on host genetic background since the congenic C3H/HeJ-lpr/lpr (C3H/lpr) mice rarely develop them. To identify the gene loci affecting each lesion, a genetic dissection of these complex pathological manifestations was carried out. First, histopathological features in MRL/lpr, C3H/lpr, (MRL/lpr x C3H/lpr) F1 intercross, and MRL/lpr x (MRL/lpr x C3H/lpr) F1 backcross mice were analyzed. Genomic DNA of the backcross mice were subjected to association studies by Chi-squared analysis for determining which polymorphic microsatellite locus occurs at higher frequency among affected compared to unaffected individuals for each lesion. As a result, gene loci recessively associated with each lesion were mapped on different chromosomal positions. We concluded that each of these lesions in MRL/lpr mice is under the control of a different set of genes, suggesting that the complex pathological manifestations of collagen disease result from polygenic inheritance.
KW - Animal model
KW - Arthritis
KW - Glomerulonephritis
KW - Mouse genetics
KW - Sialoadenitis
KW - Vasculitis
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U2 - 10.1046/j.1440-1827.1999.00979.x
DO - 10.1046/j.1440-1827.1999.00979.x
M3 - Article
C2 - 10594844
AN - SCOPUS:0033452605
VL - 49
SP - 974
EP - 982
JO - Acta Pathologica Japonica
JF - Acta Pathologica Japonica
SN - 1320-5463
IS - 11
ER -