Mechanism of bone and cartilage proliferation by a novel bone elongation factor FAM111A

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kitanaka Sachiko 東京大学, 医学部附属病院, 病院診療医(出向) (30431638)
• Co-Investigator(Kenkyū-buntansha): 齋藤 琢 東京大学, 医学部附属病院, 准教授 (30456107)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Kenny-Caffey症候群 / Osteocraniostenosis / 軟骨内骨化 / 遺伝子改変マウス

Outline of Final Research Achievements

Kenny-Caffey syndrome (KCS) is a syndrome characterized by severe short stature and delayed closure of the anterior fontanel. We previously identified that mutation in FAM111A is associated with KCS2, however, there is little knowledge of physiological function of FAM111A on skeletal tissue. We showed that overexpressing mutated human FAM111A in mice cause dramatic shortening of the limbs and delayed closure of the anterior fontanel. Furthermore, we found that FAM111A protein is processed to fragments and this processing fragments are markedly increased in the mutants. These results demonstrated that mutated FAM111A suppresses chondrocyte and osteoblast differential proliferation leading to KCS2 phenotype.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

機能不明の原因遺伝子FAM111Ａが、実際にKCS2の発症にかかわることを立証した。さらにFAM111Ａが、骨軟骨の抑制に直接かかわることを初めて示した。低身長にかかわる新たな因子の機序解明、骨成長におけるネットワーク機構の解明につながる、重要な研究成果と考える。