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10.1534/genetics.116.197376

http://scihub22266oqcxt.onion/10.1534/genetics.116.197376
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C5499168!5499168!28450461
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suck abstract from ncbi


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pmid28450461      Genetics 2017 ; 206 (2): 1139-51
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  • Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function #MMPMID28450461
  • Chen TD; Rotival M; Chiu LY; Bagnati M; Ko JH; Srivastava PK; Petretto E; Pusey CD; Lai PC; Aitman TJ; Cook HT; Behmoaras J
  • Genetics 2017[Jun]; 206 (2): 1139-51 PMID28450461show ga
  • Crescentic glomerulonephritis (Crgn) is a complex disorder where macrophage activity and infiltration are significant effector causes. In previous linkage studies using the uniquely susceptible Wistar Kyoto (WKY) rat strain, we have identified multiple crescentic glomerulonephritis QTL (Crgn) and positionally cloned genes underlying Crgn1 and Crgn2, which accounted for 40% of total variance in glomerular inflammation. Here, we have generated a backcross (BC) population (n = 166) where Crgn1 and Crgn2 were genetically fixed and found significant linkage to glomerular crescents on chromosome 2 (Crgn8, LOD = 3.8). Fine mapping analysis by integration with genome-wide expression QTLs (eQTLs) from the same BC population identified ceruloplasmin (Cp) as a positional eQTL in macrophages but not in serum. Liquid chromatography-tandem mass spectrometry confirmed Cp as a protein QTL in rat macrophages. WKY macrophages overexpress Cp and its downregulation by RNA interference decreases markers of glomerular proinflammatory macrophage activation. Similarly, short incubation with Cp results in a strain-dependent macrophage polarization in the rat. These results suggest that genetically determined Cp levels can alter susceptibility to Crgn through macrophage function and propose a new role for Cp in early macrophage activation.
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