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Updated: Sep 30, 2026
Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease
Published on: June 17, 2013
Phosphodiesterase 1B knock-out mice exhibit exaggerated locomotor hyperactivity and DARPP-32 phosphorylation in
Tracy M Reed1, David R Repaske, Gretchen L Snyder
1Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.
Abstract:
Using homologous recombination, we generated mice lacking phosphodiesterase-mediated (PDE1B) cyclic nucleotide-hydrolyzing activity. PDE1B(-/-) mice showed exaggerated hyperactivity after acute D-methamphetamine administration. Striatal slices from PDE1B(-/-) mice exhibited increased levels of phospho-Thr34 DARPP-32 and phospho-Ser845 GluR1 after dopamine D1 receptor agonist or forskolin stimulation. PDE1B(-/-) and PDE1B(+/-) mice demonstrated Morris maze spatial-learning deficits. These results indicate that enhancement of cyclic nucleotide signaling by inactivation of PDE1B-mediated cyclic nucleotide hydrolysis plays a significant role in dopaminergic function through the DARPP-32 and related transduction pathways.
