Facilitated stimulus-response associative learning and long-term memory inmice lacking the NTAN1 amidase of the N-end rule pathway

The N-end rule relates the in vivo half-life of a protein to the identity o f its N-terminal residue. Inactivation of the NTAN1 gene encoding the aspar agine-specific N-terminal amidase in mice results in impaired spatial memor y [26]. The studies described here were designed to further characterize th e effects upon learning and memory of inactivating the NTAN1 gene. NTAN1-de ficient mice were found to be better than wild-type mice on black-white and horizontal-vertical discrimination learning. They were also better at 8-we ek Morris maze retention testing when a reversal trial was not included in the testing procedures. In all three casks NTAN1-deficient mice appeared to use a strong win-stay strategy. It is concluded that inactivating the aspa ragine-specific branch of the N-end rule pathway in mice results in impaire d spatial learning with concomitant compensatory restructuring of the nervo us system in favor of non-spatial (stimulus-response) learning. (C) 2001 El sevier Science B.V. All rights reserved.