Genetic dissection of the complex pathological manifestations of collagen disease in MRL/lpr mice
Miho Terada
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorMiyuki Nishihara
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorJunji Kamogawa
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorTatsuhiko Miyazaki
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorWei-Min Qu
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorMitsuko R. Ito
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai,
Search for more papers by this authorShiro Mori
Second Department of Oral and Maxillofacial Surgery, Tohoku University School of Dentistry, Sendai and
Search for more papers by this authorYusuke Nakamura
Human Genome Center, University of Tokyo, Tokyo, Japan
Search for more papers by this authorMasato Nose
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorMiho Terada
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorMiyuki Nishihara
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorJunji Kamogawa
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorTatsuhiko Miyazaki
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorWei-Min Qu
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorMitsuko R. Ito
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai,
Search for more papers by this authorShiro Mori
Second Department of Oral and Maxillofacial Surgery, Tohoku University School of Dentistry, Sendai and
Search for more papers by this authorYusuke Nakamura
Human Genome Center, University of Tokyo, Tokyo, Japan
Search for more papers by this authorMasato Nose
Second Department of Pathology, Ehime University School of Medicine, Ehime,
Search for more papers by this authorAbstract
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 × C3H/lpr) F1 intercross, and MRL/lpr × (MRL/lpr × 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.
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