The search for modifying genetic factors for phenotypes of adrenoleukodystrophy and application to personalized medicine

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17001
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Matsukawa Takashi 東京大学, 医学部附属病院, 助教 (80755760)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 副腎白質ジストロフィー

Outline of Final Research Achievements

We were able to show that general Abcd1 knockout mice (hemizygous) and wild-type mice have different survival rates. In addition, we crossed general ABCD1 knockout mice with oligodendrocyte specific PEX5 conditional knockout mice using the Cre-loxP system mice (PEX5flox/flox*CNP-Cre/WT*ABCD1-/Y) and compared to oligodendrocyte specific PEX5 conditional knockout mice to see if there were any phenotypic differences. We checked for elevated plasma levels of very long chain fatty acids in each mouse.

Free Research Field

神経遺伝

Academic Significance and Societal Importance of the Research Achievements

副腎白質ジストロフィー（Adrenoleukodystrophy: ALD）は、ABCD1を原因遺伝子とするX連鎖遺伝性の神経変性疾患である。中枢神経の炎症性脱髄を来し、時に副腎不全を認める。様々な臨床病型を認めるが、遺伝子表現型連関は明らかでない。予後不良である大脳型に対しては早期の造血幹細胞移植が症状進行停止に有効であり、大脳型を生じやすい背景因子を同定することができれば、臨床上有用となる。