Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8

作者：Braun Doreen; Wirth Eva K; Wohlgemuth Franziska; Reix Nathalie; Klein Marc O; Grueters Annette; Koehrle Josef; Schweizer Ulrich^*

来源：Biochemical Journal, 2011, 439: 249-255.

DOI：10.1042/BJ20110759

• brain
• monocarboxylate transporter 8 (Mct8)
• system L amino acid transporter 2 (Lat2)
• 3,3',5,5'-tetra-iodo-L-thyronine (T(4))
• thyroid-stimulating hormone (TSH)
• 3,5,5'-tri-iodo-L-thyronine(T(3))

LAT2 (system L amino acid transporter 2) is composed of the subunits Slc7a8/Lat2 and Slc3a2/4F2hc. This transporter is highly expressed along the basolateral membranes of absorptive epithelia in kidney and small intestine, but is also abundant in the brain. Lat2 is an energy-independent exchanger of neutral amino acids, and was shown to transport thyroid hormones. We report in the present paper that targeted inactivation of Slc7a8 leads to increased urinary loss of small neutral amino acids. Development and growth of Slc7a8(-/-) mice appears normal, suggesting functional compensation of neutral amino acid transport by alternative transporters in kidney, intestine and placenta. Movement coordination is slightly impaired in mutant mice, although cerebellar development and structure remained inconspicuous. Circulating thyroid hormones, thyrotropin and thyroid hormone-responsive genes remained unchanged in Slc7a8(-1-) mice, possibly because of functional compensation by the thyroid hormone transporter Mct8 (monocarboxylate transporter 8), which is co-expressed in many cell types. The reason for the mild neurological phenotype remains unresolved.

• 出版日期2011-10-15