Development of animal model mimicking ornithine transcarbamylase deficiency

2014 Fiscal Year Final Research Report

• Project/Area Number: 26670383
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: CHAYAMA KAZUAKI 広島大学, 医歯薬保健学研究院(医), 教授 (00211376)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: ｹﾞﾉﾑ

Outline of Final Research Achievements

There are several liver diseases caused by genetic disorder such as Wilson’s disease, hereditary hemochromatosis and so on. One of such diseases, ornithine transcarbamylase (OTC) deficiency is caused by mutations in the OTC gene, which is located on the X chromosome. Knockout mouse is often used to study such disorders. However, the metabolism of mouse is different from that of humans. We attempted to develop a mouse model of OTC deficiency using human hepatocyte chimeric mouse. Using genome editing technology we will be able to ablate the gene to make OTC deficient liver cells. We confirmed that TALEN which cut target gene in liver cancer cell lines actually worked and also developed a method to confirm if the gene of interest had actually been ablated. This mouse model will be useful to study human liver situation in mice and will be useful to develop therapy for this disorder.

Free Research Field

肝臓病学