Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice.
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 Sjögren'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.
Nakatsuru
S
S
KAN Research Institute, Kyoto, Japan.
Terada
M
M
Nishihara
M
M
Kamogawa
J
J
Miyazaki
T
T
Qu
W M
WM
Morimoto
K
K
Yazawa
C
C
Ogasawara
H
H
Abe
Y
Y
Fukui
K
K
Ichien
G
G
Ito
M R
MR
Mori
S
S
Nakamura
Y
Y
Nose
M
M
D000818:Animals; D001167:Arteritis / Q000235:genetics / Q000473:pathology; D001168:Arthritis / Q000235:genetics / Q000473:pathology; D002875:Chromosomes / Q000235:genetics; D003095:Collagen Diseases / Q000235:genetics* / Q000473:pathology*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D012793:Sialadenitis / Q000235:genetics / Q000473:pathology