LAT1 (Slc7a5) null mice are embryonic lethal and exhibit neural tube defects (896.5)

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...