Premium
LAT1 (Slc7a5) null mice are embryonic lethal and exhibit neural tube defects (896.5)
Author(s) -
Poncet Nadege,
Shi YunBo,
Taylor Peter,
Storey Kate
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.896.5
Subject(s) - neural tube , biology , microbiology and biotechnology , neurulation , embryo , embryogenesis , endocrinology , medicine , gastrulation
The System L1‐type amino acid transporter (LAT1; catalytic subunit Slc7a5) mediates transport of large neutral amino acids (LNAA) and thyroid hormone (TH). Some LNAA are required for full activation of the mTOR‐S6K pathway promoting protein synthesis and tissue growth. TH signalling is an important regulator of embryonic development. We generated transgenic mice with functional deletion of Slc7a5. Inter‐crossing Slc7a5+/‐ mice failed to produce Slc7a5‐/‐ offspring, indicating that Slc7a5‐knockout is embryonic lethal. Fifty‐nine embryos from such crosses analysed at E9.5 to 11.5dpc (days post coitus) showed normal Mendelian distribution: 25.4% Slc7a5‐/‐, 54.2% Slc7a5+/‐, 20.4% Slc7a5+/+. At 11.5dpc, Slc7a5‐/‐ embryos were dead, but earlier stages had beating hearts. Slc7a5‐/‐ embryos exhibited defects in neural development at 9.5/10.5dpc: 20% show a “flat‐top” brain phenotype similar to that seen in mTOR deficit embryos, while 80% exhibit a failure of anterior neural tube closure and a cruciform morphology in the caudal neural tube indicative of a neurulation defect. These preliminary data suggest an essential role of Slc7a5 in embryonic development. Further studies are now required to establish the exact cause of death, the relative importance of LNAA and TH transport by Slc7a5 for embryonic development and the mechanism by which such signalling regulates neurulation. Grant Funding Source : Supported by the Wellcome Trust