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Two enzymes with NAAG peptidase activity have been cloned, glutamate carboxypeptidase II and glutamate carboxypeptidase III

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By crossing a mouse model of DS (the Tc1 mouse) that does not have an additional copy of APP to a transgenic mouse overexpressing APP with AD-causing mutations (J20 mouse), the additional copy of Hsa21, independent of an extra copy of APP , exacerbated Aβ aggregation and deposition, enhanced APP transgene-associated mortality, altered behavior, and reduced cognitive performance in double-mutant progeny that model DSAD (477)