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

Summary The spontaneous crescentic glomerulonephritis‐forming/ K injoh ( SCG / K j) 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 ( C 57 BL /6 ×  SCG / K j) F 2 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, F 4/80 + cells, CD 3 + CD 4 − CD 8 − T cells and dendritic cells ( DC s) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F 4/80 low cells were observed in crescent, while F 4/80 high cells were around the B owman's capsules and in the interstitium. Numbers of F 4/80 + cells in crescents correlated significantly with F 4/80 + cell numbers in PB , but not with numbers of F 4/80 + cells in the interstitium. Genome‐wide quantitative trait locus ( QTL ) mapping revealed three SCG / K j‐derived non‐ F as   QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTL s on chromosome 1 affected DCs , granulocytes and F 4/80 + cells, but QTL on chromosome 17 affected DC s and granulocytes. We found CrGN ‐associated leucocytes and susceptibility QTLs with their positional candidate genes. F 4/80 + 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.