GLUTAMATE TRANSPORTER EAAC-1-DEFICIENT MICE DEVELOP DICARBOXYLIC AMINOACIDURIA AND BEHAVIORAL ABNORMALITIES BUT NO NEURODEGENERATION

Four L-glutamate neurotransmitter transporters, the three Na+-dependen t 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 pi votal functions in the regulation of synaptic L-glutamate concentratio n during neurotransmission and are believed to prevent glutamate neuro toxicity. To investigate the specific physiological and pathophysiolog ical role of the neuronal EAAC-1, which is also expressed in kidney an d small intestine, we have generated two independent mouse lines lacki ng EAAC-1, eaac-1(-/-) mice develop dicarboxylic aminoaciduria. No neu rodegeneration has been observed during a period of >12 months, but ho mozygous mutants display a significantly reduced spontaneous locomotor activity.