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IA-2/IA-2ß null mice: alterations in behavior and learning

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center




  • G Carmona
  • T Nishimura
  • A Notkins


Background and Aims. IA-2 and IA-2ß are dense core vesicle (DCV) transmembrane proteins that are highly expressed in neuroendocrine cells. The knockout (KO) of IA-2 and IA-2ß results in impaired secretion of hormones and neurotransmitters. Based on these findings we hypothesized that the KO of IA-2 and/or IA-2ß would result in alterations in behavior and learning. Major Findings. In the IA-2/IA-2ß double knockout (DKO) mice, tests for evaluating anxiety-like and depression-like behavior revealed decreased exploratory activity, reduced rearing, reduced travel distance and impaired latency to descend from an elevated platform (P< 0.01 to <0.001). In classical conditioning experiments, the DKO mice showed accelerated extinction of conditioned taste aversion. In active avoidance (AA) experiments, the wild type (WT) mice showed 60-70% AA, whereas the DKO mice showed less than 10% AA. IA-2ß KO mice showed AA learning equal to WT mice, but the IA-2 KO mice failed to learn in the AA test. GBR-12909, which blocks the dopamine uptake transporter, resulted in a substantial increase in AA when administered to DKO and IA-2 KO mice. Conclusion. Taken together, these studies show that the KO of IA-2 and/or IA-2ß have a profound effect on behavior and learning.

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