Participation of LRP4 postsynaptic density protein in higher nerve function

Research Project

Project/Area Number	23500441
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Neurochemistry/Neuropharmacology
Research Institution	Shinshu University
Principal Investigator	TANAHASHI Hiroshi 信州大学, 医学系研究科, 准教授 (90236654)
Co-Investigator(Kenkyū-buntansha)	SUZUKI Tatsuo 信州大学, 医学系研究科, 教授 (80162965)
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)	2011 – 2013
Project Status	Completed (Fiscal Year 2013)
Budget Amount *help	¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000) Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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 / ノックアウトマウス / リン酸化 / 腎臓欠損
Research Abstract	Lrp4 KO mice died at birth due to their inability to breathe. The mutant mice displayed syndactyly or polydactyly and 30% (29/97) bilateral and 53% (51/97) unilateral kidney agenesis. At E18.5 the mutant lungs were reduced in size (to 88%) compared with their wild type and heterozygote counterparts, and the mutant fetus had a 2.5-times greater volume of amniotic fluid than the controls. Although the major source of fluid entering the amniotic cavity is fetal urine, the polyhydramnios were observed in the mutant fetus with bilateral kidney agenesis. The system of amniotic fluid production may be different between human and mice. The two primary routes of amniotic fluid removal are fetal swallowing and absorption from the amniotic cavity into the fetal blood vessels of the chorionic plate. The mutant fetus displayed failure to swallowing, and the expression of AQP9 and 1 were reduced in fetal membrane and placenta, respectively. We also observed Lrp4 was expressed in reactive astrocyte.