Elucidation of the mechanism of endothelin type A receptor gene disorder by animal model

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15254
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: KURIHARA Yukiko 東京大学, 大学院医学系研究科(医学部), 講師 (80345040)
• Co-Investigator(Renkei-kenkyūsha): KURIHARA Hiroki 東京大学, 大学院医学系研究科, 教授 (20221947)
• Research Collaborator: MASUDA Sho 東京大学, 大学院医学系研究科, 大学院生 ; Amiel Jeanne INSERM, Institute Imagine, Universite Paris Descartes-Sorbonne, Necker小児病院, PI ; Gordon Christopher T. INSERM, Institute Imagine, Universite Paris Descartes-Sorbonne, Necker小児病院, 研究員
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: endothelin A receptor / 顎顔面異常症 / GPCR

Outline of Final Research Achievements

One of the causative gene of human congenital anomaly, Mandibulofacial Dysostosis with Alopecia is a single nucleotide mutation of endothelin A receptor (ETAR). In this study, we generated the mutant mouse model and endothelin 3 (ET3) knockout mice using CRISPR/CAS and showed that the cause of MFDA was gain-of-function of mutant ETAR through ET3. The pharmacological experiments revealed that it is due to the enhancement of ligand binding affinity for ET3.

Free Research Field

分子生物学