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dc.contributor.advisorThe GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [3 H]taurine. Furthermore, most of the uptake of [3 H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain.
dc.contributor.authorZhou, Yun
dc.contributor.authorHolmseth, Silvia
dc.contributor.authorGuo, C
dc.contributor.authorHassel, Bjørnar
dc.contributor.authorHöfner, G
dc.contributor.authorHuitfeldt, Henrik
dc.contributor.authorWanner, KT
dc.contributor.authorDanbolt, Niels Christian
dc.date.accessioned2017-11-06T12:15:16Z
dc.date.accessioned2017-11-13T10:24:53Z
dc.date.available2017-11-06T12:15:16Z
dc.date.available2017-11-13T10:24:53Z
dc.date.issued2012
dc.identifier.citationZhou Y, Holmseth S, Guo, Hassel B, Höfner, Huitfeldt H, Wanner, Danbolt NC. Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents. Journal of Biological Chemistry. 2012;287(42):35733-35746
dc.identifier.urihttp://hdl.handle.net/20.500.12242/794
dc.identifier.urihttps://ffi-publikasjoner.archive.knowledgearc.net/handle/20.500.12242/794
dc.description-
dc.description.abstractThe GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [3H]taurine. Furthermore, most of the uptake of [3H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain.
dc.language.isoeng
dc.subjectTermSet Emneord::Hjernen
dc.subjectTermSet Emneord::Aminosyrer
dc.titleDeletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents
dc.date.updated2017-11-06T12:15:16Z
dc.identifier.cristinID973583
dc.identifier.doi10.1074/jbc.M112.368175
dc.source.issn0021-9258
dc.source.issn1083-351X
dc.type.documentJournal article
dc.relation.journalJournal of Biological Chemistry


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