Dataset Information

Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function.

ABSTRACT: 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.

SUBMITTER: Chen TD

PROVIDER: S-EPMC5499168 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function.

Chen Tai-Di TD Rotival Maxime M Chiu Ling-Yin LY Bagnati Marta M Ko Jeong-Hun JH Srivastava Prashant K PK Petretto Enrico E Pusey Charles D CD Lai Ping-Chin PC Aitman Timothy J TJ Cook H Terence HT Behmoaras Jacques J

Genetics 20170426 2

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 ...[more]

PMID: 28450461

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Dataset Information

Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function.

Publications

Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function.

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