Elucidation of the mechanism to improve the cleft palate phenotype with the molecular target drug

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Asahi University
• Principal Investigator: TAKIGAWA Toshiya 朝日大学, 歯学部, 教授 (90263095)
• Co-Investigator(Kenkyū-buntansha): INTO Takeshi 朝日大学, 歯学部, 講師 (10360918) ; TAKAGI Shuta 朝日大学, 歯学部, 元助教 (10711351)
• Research Collaborator: SUGIYAMA Akiko 朝日大学, 歯学部, 助教 (90304534)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 口蓋裂 / TGFβ3ノックアウトマウス / 分子標的治療薬 / エピジェネティクス / シグナル伝達系

Outline of Final Research Achievements

Even if the mice as well as humans carry the same gene mutation, the phenotype differs dependently on the genetic background, but its cause remained enigmatic. This study showed that the phenotype of the genetically induced palatal cleft is dependent on epigenetic modifiers, such as the balance in the expression level of IGF2R and various activated signaling molecules, by using two different strains of TGFβ3 knockout mice. Furthermore, we demonstrated for the first time that administration of molecular target drugs against DNA methyltransferase and epidermal growth factor receptor can improve the severity of the palatal cleft via the elevated expression of IGF2R and the reduced expression of phospho-Erk1/2, respectively. These findings provide insight into new strategies of preventive pharmacological fetal therapy in addition to postnatal surgery against human palatal cleft, to improve the severity of the fetal phenotype of pregnant woman with gene mutation of causing palatal cleft.

Free Research Field

発生学／口腔解剖学