Development and application of mouse model of Phldb1 mutation associated with multiple diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: WADA Kenta 東京農業大学, 生物産業学部, 准教授 (20508113)
• Co-Investigator(Kenkyū-buntansha): 松岡 邦枝 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (40291158)
• Research Collaborator: KIKKAWA Yoshiaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 白内障 / 水晶体脱臼 / PHLDB1

Outline of Final Research Achievements

The rlc2 mouse spontaneously exhibits lens opacity with luxation of lens nuclei, which is caused by a 1-bp insertion on the Phldb1 gene. At 2 months of age, disruption of posterior lens capsule was found in transparent lens of rlc2 mouse. Therefore, we concluded that lens opacity was caused by luxation of lens nuclei. In wild-type, PHLDB1 protein detected on anterior lens capsule of embryonic day 15.5 and postnatal day 1, and that extended to posterior capsule at postnatal day 5. The expression of PHLDB1 could not be observed in rlc2 lens capsule. Therefore, we suggested that rupture of lens capsule of rlc2 mouse was caused by a large reduction of PHLDB1 protein on lens capsule. Transcriptome analysis detected many differentially expressed genes between wild-type and rlc2 lenses. We speculated that these differentially expressed genes caused by reduction of PHLDB1 protein have roles for maintenance of lens capsule. Our results would provide new insight of PHLDB1 function on the lens.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、ヒト疾患との関連性が示唆されているものの、その生体内（in vivo）における機能が明らかになっていないPHLDB1が、水晶体カプセルの維持に機能することをモデル動物の解析に基づいて明らかにした初めての研究である。このことは、本研究の成果と、rlc2マウスがPHLDB1のin vivoにおける機能について、新たな知見を提供することを示している。