Effect of SLAM mutation and activating and inhibitory FcR on autoimmune prone mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: TAKASAKI Yoshinari 順天堂大学, 医学部, 特任教授 (80154772)
• Co-Investigator(Renkei-kenkyūsha): HIROSE Sachiko 桐蔭横浜大学, 工学部, 客員研究員 (00127127)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: SLE / Slam / Yaa / Fc receptor / モデルマウス

Outline of Final Research Achievements

We previously obtained a 129-derive FcγRIIB-deficient C57BL/6 (B6) congenic strain of mice, which developed rheumatoid arthritis (RA). The introduction of the Yaa (Y-linked autoimmune acceleration) mutation (Tlr7 gene duplication) to the FcγRIIB-deficient B6 mice(B6.FcγRIIB-/-.Yaa ) developed lupus like nephritis but not RA. By extensive backcrossing, we established wildtype FcγRIIB and 129-derive autoimmune-prone SLAM haplotype(Slam129). We examined the phenotype of the mice, and also Slam129.Yaa mice by introducing Yaa mutation. Slam129 mice did not show any pathogenic autoantibodies. When introducing Yaa mutation, Slam129.Yaa mice showed significant increase the serum levels of anti-RNP/Sm antibodies. They did not show the elevation of anti-dsDNA antibodies. Also they developed nephritis but the pathological score was significantly lower than B6.FcγRIIB-/-.Yaa mice. Autoimmune-prone Slam129.Yaa mice developed specific lupus phenotype resembling mixed connective tissue disease.

Free Research Field

Rheumatology and Immunology