Generation and analysis of in vitro, in vivo model of sideroblastic anemia

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293225
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Harigae Hideo 東北大学, 医学(系)研究科(研究院), 教授 (50302146)
• Co-Investigator(Renkei-kenkyūsha): KAWAMATA Shin 公益財団法人先端医療振興財団, 副事業統括 (00360842) ; FUJIWARA Tohru 東北大学, 大学病院, 講師 (60333796)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 内科学

Outline of Final Research Achievements

Sideroblastic anemia is characterized by anemia with ring sideroblasts in the bone marrow. In order to develop a novel therapy for sideroblastic anemia, iPS cells were established from a patient of X-linked sideroblastic anemia (XLSA), which is caused by mutations of 5-aminolevulinate synthase (ALAS2) gene. The expression profiling of erythroblasts derived from XLSA iPS cells showed that the expression levels of globins and erythroid-specific transcription factors were decreased compared to those derived from control iPS cells. When XLSA derived iPS cells were co-cultured with stromal cells; aberrant mitochondrial iron deposition was detected by prussian blue staining and electron microscope analysis. In addition, XLSA model mouse has been generated by introducing mutations to the enhancer lesion of ALAS2 gene by CRISPR/CAS9 system. Mutant mice were anemic, and the expression level of ALAS2 of bone marrow was decreased. Iron metabolism and erythropoiesis are under investigation.

Free Research Field

血液内科学