Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model. 2014

Y Hamano, and M Abe, and S Matsuoka, and D Zhang, and Y Kondo, and Y Kagami, and A Ishigami, and N Maruyama, and Y Tsuruta, and W Yumura, and K Suzuki
Aging Regulation Section, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan; Department of Nephrology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan; Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007964 Leukocytosis A transient increase in the number of leukocytes in a body fluid. Pleocytosis,Leukocytoses,Pleocytoses
D008040 Genetic Linkage The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME. Genetic Linkage Analysis,Linkage, Genetic,Analyses, Genetic Linkage,Analysis, Genetic Linkage,Genetic Linkage Analyses,Linkage Analyses, Genetic,Linkage Analysis, Genetic
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009195 Peroxidase A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. Myeloperoxidase,Hemi-Myeloperoxidase,Hemi Myeloperoxidase
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260 Female Females
D005921 Glomerulonephritis Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY. Bright Disease,Kidney Scarring,Glomerulonephritides,Scarring, Kidney

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