Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration.
Four L-glutamate neurotransmitter transporters, the three Na(+)-dependent GLAST-1, GLT-1 and EAAC-1, and the Cl(-)-dependent EAAT-4, form a new family of structurally related integral plasma membrane proteins with different distribution in the central nervous system. They may have pivotal functions in the regulation of synaptic L-glutamate concentration during neurotransmission and are believed to prevent glutamate neurotoxicity. To investigate the specific physiological and pathophysiological role of the neuronal EAAC-1, which is also expressed in kidney and small intestine, we have generated two independent mouse lines lacking EAAC-1. eaac-1(-/-) mice develop dicarboxylic aminoaciduria. No neurodegeneration has been observed during a period of >12 months, but homozygous mutants display a significantly reduced spontaneous locomotor activity.
Peghini
P
P
Laboratory of Molecular Neuroscience, Institute of Biochemistry, Faculty of Medicine, University of Cologne, Germany.
Janzen
J
J
Stoffel
W
W
D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000600:Amino Acids, Dicarboxylic / Q000652:urine*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004827:Epilepsy / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1; D005260:Female; D018390:Gene Targeting; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D010433:Pentylenetetrazole; D010641:Phenotype; D051381:Rats; D027981:Symporters
D027322:Amino Acid Transport System X-AG; D000600:Amino Acids, Dicarboxylic; D002352:Carrier Proteins; D027341:Excitatory Amino Acid Transporter 1; D050491:Glutamate Plasma Membrane Transport Proteins; C493393:Slc1a3 protein, mouse; C493392:Slc1a3 protein, rat; D027981:Symporters; D018698:Glutamic Acid; D010433:Pentylenetetrazole