a molecular biology study of Autosomal dominant tubulointerstitial kidney disease by using mutated MUC1 cDNA sequence identified in our own patient family.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09615
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: Kaimori Junya 大阪大学, 医学系研究科, 寄附講座准教授 (70527697)
• Co-Investigator(Kenkyū-buntansha): 猪阪 善隆 大阪大学, 医学系研究科, 教授 (00379166) ; 高原 史郎 大阪大学, 医学系研究科, 招へい教授 (70179547) ; 市丸 直嗣 大阪大学, 医学系研究科, 寄附講座准教授 (70346211)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ADTKD / MUC1 / VNTR / 小胞体ストレス / 細胞内凝集

Outline of Final Research Achievements

Autosomal dominant tublointerstitial kidney disease (ADTKD) is an inherited kidney disease characterized by the progressive renal function loss almost without no urine sedimentation findings. Almost all previous gene mutation sites in ADTKD-MUC1 were placed within variable number tandem repeats (VNTRs). We discovered ADTKD-MUC1 family whose mutation site was before VNTRs. We also discovered that mutant MUC1 protein was resulted in cytoplasmic aggregation. Furtherly, we made mutant human MUC1 transgenic mouse and found that these mice demonstrated systemic inflammatory disease. In the response to these transgenic mouse findings, re-examination in our patients revealed that they also had interstitial pneumonia, inflammatory bowel disease, and skin lesion, which had not been described as symptoms of ADTKD-MUC1.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

従来、ADTKD-MUC1の遺伝子異常部位は、VNTRに限られており、世界的にもVNTR以外のMUC1異常は報告されてこなかった。今症例は、VNTR以前に異常のある症例であり、症例的な意義は高い。また、ADTKD-MUC1の腎外病変については、今まで世界でも報告された事は無く、ADTKD-MUC1には、腎外病変はないとされてきた。申請者らの、transgenic mouse及び患者家系における、腎外病変の発見は、ADTKD-MUC1の病態像を根底から書き換えるもので、臨床的な意義は極めて高い。