Mechanisms of Rho family proteins during cartolage and bone formation

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K11051
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Showa University
• Principal Investigator: Atsushi Yamada 昭和大学, 歯学部, 講師 (50407558)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 細胞内シグナル伝達

Outline of Final Research Achievements

We created mice with double deletion of Rac1 and Cdc42. We aimed to study the functional duplication of Rac1 and Cdc42 genes by comparing their phenotypes with those of mice. In order to specifically delete the Rac1 and Cdc42 genes in cartilage tissue, Rac1 flox mice Cdc42 flox mice and Col2 Cre transgenic mice were mated. The mice in which the Rac1 and Cdc42 genes were double deleted became lethal soon after birth, as in the case where the Cdc42 gene was single deleted. The long bones were shorter compared to the single deletion of the Rac1 and Cdc42 genes. In addition, the mice in which the Rac1 and Cdc42 genes were double deleted were found to have abnormal formation in skeletal organs. Stronger abnormalities were observed in cell composition and columnar formation in the growth plate than those of Rac1 and Cdc42 single knockout mice.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

Rhoファミリー低分子量Gタンパク質Rac1およびCdc42は細胞外からの様々な情報を細胞内に伝達する細胞内シグナル伝達因子である。主にアクチン細胞骨格制御を介した様々な生物活性、例えば細胞の増殖、分化、細胞死等を制御していることが知られている。Rac1およびCdc42の硬組織形成における機能を、組織および時期特異的に欠損させたコンディショナルノックアウトマウスを作製したところ、それぞれ共通した表現型と異なる表現型を呈した。Rac1およびCdc42をダブル欠損させたマウスを作製し、シングル欠損させたマウスと表現型を比較することによりRac1およびCdc42遺伝子の機能重複性が明らかとなった。