Participation of LRP4 postsynaptic density protein in higher nerve function

Lrp 4基因敲除小鼠在出生时由于无法呼吸而死亡。突变小鼠表现为并指或多指，30%（29/97）的小鼠双侧肾发育不全，53%（51/97）的小鼠单侧肾发育不全。在E18.5时，突变体的肺与野生型和杂合子相比缩小了88%，突变体胎儿的羊水量是对照组的2.5倍。虽然进入羊膜腔的液体主要来源是胎儿尿液，但在双肾发育不全的突变胎儿中观察到羊水过多。人类和小鼠的羊水产生系统可能不同。羊水排出的两个主要途径是胎儿吞咽和从羊膜腔吸收到绒毛膜板的胎儿血管中。突变胎儿表现为吞咽障碍，胎膜和胎盘中AQP 9和1的表达分别减少。我们还观察到Lrp 4在反应性星形胶质细胞中表达。

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.