Cognitive and Socio-Emotional Deficits in Platelet-Derived Growth Factor Receptor-β Gene Knockout Mice

Platelet-derived growth factor (PDGF) is a potent mitogen. Extensive in vivo studies of PDGF and its receptor (PDGFR) genes have reported that PDGF plays an important role in embryogenesis and development of the central nervous system (CNS). Furthermore, PDGF and the beta subunit of the PDGF receptor (PDGFR-beta) have been reported to be associated with schizophrenia and autism. However, no study has reported on the effects of PDGF deletion on mice behavior. Here we generated novel mutant mice (PDGFR-beta KO) in which PDGFR-beta was conditionally deleted in CNS neurons using the Cre/loxP system. Mice without the Cre transgene but with floxed PDGFR-beta were used as controls. Both groups of mice reached adulthood without any apparent anatomical defects. These mice were further examined by conducting several behavioral tests for spatial memory, social interaction, conditioning, prepulse inhibition, and forced swimming. The test results indicated that the PDGFR-beta KO mice show deficits in all of these areas. Furthermore, an immunohistochemical study of the PDGFR-beta KO mice brain indicated that the number of parvalbumin (calcium-binding protein)-positive (i.e., putatively gamma-aminobutyric acid-ergic) neurons was low in the amygdala, hippocampus, and medial prefrontal cortex. Neurophysiological studies indicated that sensory-evoked gamma oscillation was low in the PDGFR-beta KO mice, consistent with the observed reduction in the number of parvalbumin-positive neurons. These results suggest that PDGFR-beta plays an important role in cognitive and socioemotional functions, and that deficits in this receptor may partly underlie the cognitive and socioemotional deficits observed in schizophrenic and autistic patients.