Correction of X-linked Neutropenia(XLN) by iPS cell based new gene modified therapy

基于 iPS 细胞的新基因修饰疗法纠正 X 连锁中性粒细胞减少症 (XLN)

• 批准号: 18K16112
• 负责人: チャンダ ビディシャ
• 金额: $ 2.66万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2018
• 资助国家: 日本
• 起止时间: 2018-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-18K16112/
• 关键词: X-linked Neutropenia; iPS; Hematopoietic Stem cell; Gene Editing; X-Linked Neutropenia; Hematopoietic stem cells; Gene editing; Mouse model

In vivo XLN mouse model:Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency disorder. Mutation in WAS gene cause Wiskott-Aldrich syndrome.We performed the whole genome sequencing of the blood cells from an XLN patient and identified a novel missense mutation in the WAS gene (WASp I290T).We used CRISPER/Cas9 system to generate knock in mouse model. We successfully knocked in I292T mutation in exan 9 of WAS gene in mice which was compatible of WAS I290T human mutation.As a result we got two mutation positive male and three female mice. Then cross breeding in between them to get pure homozygous mouse for this model system.

体内XLN小鼠模型：Wiskott-Aldrich综合征（WAS）是一种X连锁原发性免疫缺陷疾病。WAS基因突变导致Wiskott-Aldrich综合征，我们对一例XLN患者的血细胞进行了全基因组测序，发现了WAS基因的一个新的错义突变（WASp I290 T），并利用CRISPER/Cas9系统建立了敲除小鼠模型。我们成功敲入了与人类WAS I290 T突变相匹配的小鼠WAS基因外显子9的I292 T突变，获得了2只突变阳性的雄性和3只突变阳性的雌性小鼠。然后在它们之间进行杂交，以获得该模型系统的纯合子小鼠。

项目成果

Functional analysis of the novel WASP mutation resulting in X-linked congenital neutropenia

导致 X 连锁先天性中性粒细胞减少症的新型 WASP 突变的功能分析

• 发表时间: 2018
• 作者: Masayuki Kobayashi,Chanda Bidisha,Muneyoshi Futami,,Mizuho Yamashita,Mitsuhiro Hirano,Kazuaki Yokoyama,Yoichi Imai;Eigo Yusa,Rui Yamaguchi,Seiya Imoto,Satoru Miyano,Arinobu Tojo
• 通讯作者: Eigo Yusa,Rui Yamaguchi,Seiya Imoto,Satoru Miyano,Arinobu Tojo