{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:34:28Z","timestamp":1790253268445,"version":"4.1.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"42","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16H06146"],"award-info":[{"award-number":["JP16H06146"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18H04891"],"award-info":[{"award-number":["JP18H04891"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25112009"],"award-info":[{"award-number":["JP25112009"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23220011"],"award-info":[{"award-number":["JP23220011"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H05758"],"award-info":[{"award-number":["JP19H05758"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,10,15]]},"abstract":"<jats:p>\n                    The placenta is critical in mammalian embryonic development because the embryo\u2019s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through it. However, the molecular mechanisms underlying this amino acid supply are poorly understood. In this study, we focused on system A amino acid transporters\n                    <jats:italic>Slc38a1<\/jats:italic>\n                    \/SNAT1,\n                    <jats:italic>Slc38a2<\/jats:italic>\n                    \/SNAT2, and\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    \/SNAT4, which carry neutral, short-side-chain amino acids, to determine their involvement in placental or embryonic development. A triple-target CRISPR screen identified\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    \/SNAT4 as the critical amino acid transporter for placental development in mice. We established mouse lines from the CRISPR founders with large deletions in\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    and found that, consistent with the imprinted paternal expression of\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    \/SNAT4 in the placenta, paternal knockout (KO) but not maternal KO of\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    \/SNAT4 caused placental hypoplasia associated with reduced fetal weight. Immunostaining revealed that SNAT4 was widely expressed in differentiating cytotrophoblasts and maturing trophoblasts at the maternal\u2013fetal interface. A blood metabolome analysis revealed that amino acid concentrations were globally reduced in\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    \/SNAT4 mutant embryos. These results indicated that SNAT4-mediated amino acid transport in mice plays a major role in placental and embryonic development. Given that expression of\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    in the placenta is conserved in other species, our\n                    <jats:italic>Slc38a4<\/jats:italic>\n                    \/SNAT4 mutant mice could be a promising model for the analysis of placental defects leading to intrauterine growth restriction in mammals.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1907884116","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T22:27:27Z","timestamp":1569882447000},"page":"21047-21053","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":64,"title":["Paternal knockout of\n                    <i>Slc38a4<\/i>\n                    \/SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0474-232X","authenticated-orcid":false,"given":"Shogo","family":"Matoba","sequence":"first","affiliation":[{"name":"Bioresource Engineering Division, Bioresource Research Center, RIKEN, 305-0074 Tsukuba, Ibaraki, Japan;"},{"name":"Cooperative Division of Veterinary Sciences, Tokyo University of Agriculture and Technology, 183-8509 Fuchu, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Nakamuta","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Iwate University, 020-8550 Morioka, Iwate, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Miura","sequence":"additional","affiliation":[{"name":"Bioresource Engineering Division, Bioresource Research Center, RIKEN, 305-0074 Tsukuba, Ibaraki, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Hirose","sequence":"additional","affiliation":[{"name":"Bioresource Engineering Division, Bioresource Research Center, RIKEN, 305-0074 Tsukuba, Ibaraki, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirosuke","family":"Shiura","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Yamanashi, 400-8510 Kofu, Yamanashi, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kohda","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Yamanashi, 400-8510 Kofu, Yamanashi, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Nakamuta","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Iwate University, 020-8550 Morioka, Iwate, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Ogura","sequence":"additional","affiliation":[{"name":"Bioresource Engineering Division, Bioresource Research Center, RIKEN, 305-0074 Tsukuba, Ibaraki, Japan;"},{"name":"Graduate School of Life and Environmental Sciences, University of Tsukuba, 305-8572 Tsukuba, Ibaraki, Japan;"},{"name":"The Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, 113-0033 Tokyo, Japan;"},{"name":"Bioresource Engineering Laboratory, RIKEN Cluster for Pioneering Research, 351-0198 Wako, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"16153","DOI":"10.3390\/ijms150916153","article-title":"Maternal-fetal nutrient transport in pregnancy pathologies: The role of the placenta","volume":"15","author":"Brett K. 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