Participation of LRP4 receptor which is indispensable to neuromuscular junctions in central nervous system

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Shinshu University
• Principal Investigator: TANAHASHI Hiroshi 信州大学, 学術研究院医学系, 准教授 (90236654)
• Co-Investigator(Renkei-kenkyūsha): SAKAGAMI Hiroyuki 北里大学, 医学部, 教授 (90261528) ; HARA Yoshinobu 北里大学, 医学部, 助教 (40558467)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経可塑性 / シナプス / 合指多指症 / 歯数過剰 / 不正咬合 / 腎臓欠失 / 羊水過多 / アクアポリン

Outline of Final Research Achievements

Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the fetal kidneys and partly on the fluid secretion from the fetal lungs during fetal breathing-like movements. Lrp4, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of Lrp4 KO mice. Most KO fetuses showed unilateral or bilateral kidney agenesis, and Lrp4 knockout resulted in polyhydramnios. The loss of Lrp4 compromised fetal swallowing and breathing-like movements and downregulated the expression of AQP9 in the fetal membrane and AQP1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in KO fetuses, resulting in polyhydramnios despite the impairment of urine production. Our findings indicate that amniotic fluid removal plays an essential role in regulating the amniotic fluid volume during mid-to-late gestation.

Free Research Field

神経科学