Responsible genes for the aberrant production of MPO-ANCA

2014 Fiscal Year Final Research Report

• Project/Area Number: 23510244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2012-2014); Jichi Medical University (2011)
• Principal Investigator: HAMANO Yoshitomo 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (10281354)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: SCG/Kj / MPO-ANCA / 血管炎 / 半月体形成性糸球体腎炎 / マッピング

Outline of Final Research Achievements

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a unique model of vasculitis with production of MPO-ANCA. Genome wide mapping revealed the non-Fas susceptibility locus of MPO-ANCA on chromosome 1, designated as Man-1. The aim of this study is to identify the responsible gene (s) of Man-1. Interval mapping created single peak of LOD curve on the Gene A, a protein-coding gene with unknown function. Because of the highest LOD score, Gene A was the first positional candidate gene. Recombinant Gene A accelerated the proliferation of murine myeloid cell line Mcl33D. However, transfection of Gene A to Mcl33D did not influenced to expression levels of leukocyte activation markers.
We established SCG/Kj-derived interval congenic mice with B6 background. Fortunately, we obtained mice with recombination between B6 and SCG/Kj at the midpoint of Man-1 interval. These mice will help us to narrow down positional candidate genes on Man-1 interval.

Free Research Field

免疫病理学