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| Status |
Public on Aug 23, 2019 |
| Title |
Paternal knockout of Slc38a4/SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The placenta is critical for mammalian embryonic development because the embryo’s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through the placenta. However, the molecular mechanisms underlying this amino acid supply are poorly understood. In this study, we focused on the system A amino acid transporters, Slc38a1/SNAT1, Slc38a2/SNAT2, and Slc38a4/SNAT4, which carry neutral, short-side-chain amino acids, to determine their involvement in placental or embryonic development. A triple-target CRISPR screen identified Slc38a4/SNAT4 as the critical amino acid transporter for placental development in mice. We established mouse lines from the CRISPR founders with large deletions in Slc38a4 and found that, consistent with the imprinted paternal expression of Slc38a4/SNAT4 in ther placenta, paternal knockout (KO), but not maternal KO, of Slc38a4/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–fetal interface. A blood metabolome analysis revealed that amino acid concentrations were globally reduced in Slc38a4/SNAT4 mutant embryos. These results indicated that, in mice, SNAT4-mediated amino acid transport plays a major role in both placental and embryonic development. Given that expression of Slc38a4 in placentas is conserved in other species, our Slc38a4/SNAT4 mutant mice could be a promising model for the analysis of placental defects leading to intrauterine growth restriction in mammals.
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| Overall design |
Global gene expression patterns in the placenta of wildtype (WT) and Slc38a4 mutant mice (MKO, PKO, and Null) were analyzed by one-color Mouse Gene Expression 8x60K microarray. RNA was extracted from E13.5 placentas using an RNeasy Mini Kit (Qiagen). Total RNA (200 ng) was amplified and labeled with a Low Input Quick Amp Gene Expression Labeling Kit (#5190-2305, Agilent Technologies). The labeled cRNA was hybridized to a mouse oligo DNA microarray (8x60K, SurePrint G3 Mouse GE v2; #G4852B, Agilent Technologies). After the scan, the signal intensities on the microarray were processed using the Feature extraction software (Agilent Technologies) and analyzed by GeneSpring 14.5 (Agilent Technologies).
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| Contributor(s) |
Matoba S, Nakamuta S, Miura K, Hirose M, Shiura H, Kohda T, Nakamuta N, Ogura A |
| Citation(s) |
31570606 |
| Submission date |
Aug 22, 2019 |
| Last update date |
Nov 22, 2019 |
| Contact name |
Shogo Matoba |
| E-mail(s) |
shogomatoba@gmail.com
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| Organization name |
RIKEN BioResource Research Center
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| Street address |
3-1-1, Koyadai
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| City |
Tsukuba |
| State/province |
Ibaraki |
| ZIP/Postal code |
305-0074 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA561605 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136212_RAW.tar |
36.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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