Carboxypeptidase E knockout mice exhibit abnormal dendritic arborization and spine morphology in central nervous system neurons

Carboxypeptidase E (CPE) is involved in maturation of neuropeptides and sorting of brain‐derived neurotrophic factor (BDNF) to the regulated pathway for activity‐dependent secretion from CNS neurons. CPE knockout (CPE‐KO) mice have many neurological deficits, including deficits in learning and memory. Here, we analyzed the dendritic arborization and spine morphology of CPE‐KO mice to determine a possible correlation of defects in such structures with the neurological deficits observed in these animals. Analysis of pyramidal neurons in layer V of cerebral cortex and in hippocampal CA1 region in 14‐week‐old CPE‐KO mice showed more dendritic complexity compared with wild type (WT) mice. There were more dendritic intersections and more branch points in CPE‐KO vs. WT neurons. Comparison of pyramidal cortical neurons in 6‐ vs. 14‐week‐old WT mice showed a decrease in dendritic arborization, reflecting the occurrence of normal dendritic pruning. However, this did not occur in CPE‐KO neurons. Furthermore, analysis of spine morphology demonstrated a significant increase in the number of D‐type spines regarded as nonfunctional in the cortical neurons of CPE‐KO animals. Our findings suggest that CPE is an important, novel player in mediating appropriate dendritic patterning and spine formation in CNS neurons. © 2009 Wiley‐Liss, Inc.