Disease modeling of Down syndrome using human iPSC and genome-editing technologies

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860799
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: Hirata Katsuya 大阪大学, 医学部附属病院, 医員 (30724306)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: iPS細胞 / ゲノム編集 / ダウン症候群

Outline of Final Research Achievements

Children with Down syndrome (DS) are predisposed to developing transient myeloproliferative disorder (TMD) which are supposed to be caused by constitutive trisomy 21 and acquired mutations in X-linked GATA1 gene. These mutations lead to production of a variant GATA1 protein that is truncated at its N terminus. To clarify each pathogenic role of trisomy 21 and GATA1 short form in TMD, we aimed to generate precise disease model.
We created human induced pluripotent stem cells (iPSCs) from mononuclear cells of a male TMD neonate with somatic hemizygous mutation in GATA1 as well as iPSCs of the same patient without the mutation. Using TALE nucleases (TALENs), we obtained various iPSC lines with normal GATA1, GATA1 short and GATA1-null from Trisomy 21 and normal karyotype male. Our experimental model using human disease specific iPSCs and gene targeting system will be a powerful tool in studying the several congenital disease pathogenesis in pediatric research field.

Free Research Field

幹細胞研究