Paternal knockout of Slc38a4 /SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice

• DOI: 10.1073/pnas.1907884116
• Publication Date: 2019-10-01T02:27:27Z
• Authors: Shogo Matoba; Shoko Nakamuta; Kento Miura; Michiko Hirose; Hirosuke Shiura; Takashi Kohda; Nobuaki Nakamuta; Atsuo Ogura
• Keywords: Intrauterine growth restriction; Amino acid transporter; Immunostaining; Placentation

The placenta is critical in mammalian embryonic development because the embryo’s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through it. However, molecular mechanisms underlying this acid are poorly understood. In study, we focused system A transporters Slc38a1 /SNAT1, Slc38a2 /SNAT2, and Slc38a4 /SNAT4, which carry neutral, short-side-chain to determine their involvement placental or development. triple-target CRISPR screen identified /SNAT4 as transporter for mice. We established mouse lines from founders with large deletions found that, consistent imprinted paternal expression placenta, knockout (KO) but not maternal KO caused hypoplasia associated reduced fetal weight. Immunostaining revealed that SNAT4 was widely expressed differentiating cytotrophoblasts maturing trophoblasts at maternal–fetal interface. blood metabolome analysis concentrations were globally mutant embryos. These results indicated SNAT4-mediated mice plays a major role Given conserved other species, our could be promising model defects leading intrauterine growth restriction mammals.