Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents
Open accessAbstract
The 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.
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Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons
Alves de Lima, K., Rustenhoven, J., Da Mesquita, S., Wall, M., Salvador, A. F., Smirnov, I., Martelossi Cebinelli, G., Mamuladze, T., Baker, W., Papadopoulos, Z., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0776-4 · Cited by 416 · see citing works
- Authors
- Zhou, Y., Holmseth, S., Guo, C., Hassel, B., Höfner, G., Huitfeldt, H. S., Wanner, K. T., & Danbolt, N. C.
- Affiliations
- University of Oslo (NO)
- Howard Hughes Medical Institute (US)
- Oslo University Hospital (NO)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Danbolt, Niels C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 287
- Issue
- 42
- Pages
- 35733-35746
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3471754
- OpenAlex
- W1566384403
- Cited by
- 102
- References
- 91
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 12 · 2013: 4 · 2012: 2
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- GABA transporters, knockout mice, taurine transport, hepatocytes, proximal tubule, GABA uptake, leptomeninges
- MeSH terms
- Animals, Brain, Brain Chemistry, Humans, Kidney Cortex, Kidney Tubules, Proximal, Liver, Male, Rabbits, Taurine, Rats, Wistar, Mice, Knockout, Hepatocytes, GABA Plasma Membrane Transport Proteins, Mice, Rats, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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