Research strategy for identification of the pathogenesis of the common structural abnormalies in craniomaxillofacial region

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293436
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: TANAKA Eiji 徳島大学, 大学院医歯薬学研究部, 教授 (40273693)
• Co-Investigator(Kenkyū-buntansha): 井本 逸勢 徳島大学, 大学院医歯薬学研究部, 教授 (30258610) ; 泰江 章博 徳島大学, 大学病院, 講師 (80380046)
• Research Collaborator: MITSUI Naomi 徳島大学, 大学院医歯薬学研究部, ポスドク
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ゲノム編集 / 遺伝子疾患 / CRISPR/Cas / 非症候性多数歯欠損

Outline of Final Research Achievements

Non-syndromic tooth agenesis has been associated with mutation in a variety of genes involved in tooth morphogenesis. We identified a novel frameshift mutation of the highly conserved C-terminal domain of MSX1, known as Msx homology domain 6 (MH6), in a Japanese family with non-syndromic tooth agenesis. To investigate the importance of MH6 in tooth development, Msx1 was targeted in mice with a CRISPR/Cas system. Although heterozygous MH6 disruption did not alter normal craniofacial development, homozygous mice exhibited agenesis of lower incisors with or without cleft palate at E16.5. In addition, agenesis of the upper third molars and the lower second and third molars were observed in 4-week-old mutant mice. Although the upper second molars were present, they were abnormally small. These results suggest that the C-terminal domain of MSX1 is important for tooth and palate development.

Free Research Field

医歯薬学