Study on molecular pathogenesis of X-linked neutropenia and WIP deficiency by using NOG mice and human myeloid cell line.

2014 Fiscal Year Final Research Report

• Project/Area Number: 23591528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: SASAHARA Yoji 東北大学, 医学(系)研究科(研究院), 准教授 (60372314)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: WASP / WIP / 原発性免疫不全症 / ヒト化マウス / NOGマウス

Outline of Final Research Achievements

Rare gain-of-function mutations in the WASP gene are known to result in X-linked neutropenia (XLN). We first tried transdution of mutant WASP and WIP genes into CD34 positive human hematopoietic stem cells. However, transduction efficiency was very low. Therefore we next performed experiments by using myeloid cell line K562.
We reported that a part of WASP localized in the nucleus and a tendency of activating WASP mutants to localize in the nucleus more than WT. We found that WASP could form a complex with RNA polymerase II. To determine whether gene transcription was affected by WASP mutants in myeloid cells, we performed microarray analysis and found different expression profiles between WT and L270P WASP-transfected K562 cells. Among the genes affected, granulocyte colony-stimulating factor receptor(G-CSFR) and Runx1 were included. Therefore, our results suggested that open conformation of WASP would contribute to the outcome of myeloid cell differentiation and pathogenesis of XLN.

Free Research Field

小児血液腫瘍学、原発性免疫不全症