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Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and\/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. <jats:italic>Lrp4<\/jats:italic>, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of <jats:italic>Lrp4<\/jats:italic> knockout (<jats:italic>Lrp4<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice. Most <jats:italic>Lrp4<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> foetuses showed unilateral or bilateral kidney agenesis and <jats:italic>Lrp4<\/jats:italic> knockout resulted in polyhydramnios. The loss of <jats:italic>Lrp4<\/jats:italic> compromised foetal swallowing and breathing-like movements and downregulated the expression of aquaporin-9 in the foetal membrane and aquaporin-1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in <jats:italic>Lrp4<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> foetuses, 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.<\/jats:p>","DOI":"10.1038\/srep20241","type":"journal-article","created":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T10:29:58Z","timestamp":1454668198000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance"],"prefix":"10.1038","volume":"6","author":[{"given":"Hiroshi","family":"Tanahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Bao","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sakagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Endo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,5]]},"reference":[{"key":"BFsrep20241_CR1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-4939-1031-1_5","volume":"814","author":"RA Brace","year":"2014","unstructured":"Brace, R. 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