title: Aminoaciduria, but normal thyroid hormone levels and signalling, in mice lacking the amino acid and thyroid hormone transporter Slc7a8.
abstract: 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 co-ordination 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(-/-) 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.
authors: Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Doreen
authors: D
authors: Braun
authors: Eva K
authors: EK
authors: Wirth
authors: Franziska
authors: F
authors: Wohlgemuth
authors: Nathalie
authors: N
authors: Reix
authors: Marc O
authors: MO
authors: Klein
authors: Annette
authors: A
authors: Grüters
authors: Josef
authors: J
authors: Köhrle
authors: Ulrich
authors: U
authors: Schweizer
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood*; D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development; D017931:DNA Primers; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D027182:Amino Acid Transport System y+; D017931:DNA Primers; D027301:Fusion Regulatory Protein 1, Light Chains; C518286:SLC7A8 protein, mouse; D013963:Thyroid Hormones