Rescuing Impairment of Long-Term Potentiation in Fyn-Deficient Mice by Introducing Fyn Transgene

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-04, Vol.94 (9), p.4761-4765
• Main Authors: Kojima, Nobuhiko, Wang, Jian, Mansuy, Isabelle M., Seth G. N. Grant, Mayford, Mark, Kandel, Eric R.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Biological Sciences; Cellular biology; Complementary DNA; Deoxyribonucleic acid; DNA; Forebrain; Hippocampus - abnormalities; Hippocampus - cytology; Hippocampus - physiology; Long term potentiation; Long-Term Potentiation - genetics; Messenger RNA; Mice; Mice, Transgenic; Neurology; Neurons; Neurons - physiology; Phenotypes; Protein-Tyrosine Kinases - deficiency; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins c-fyn; Proto-Oncogene Proteins pp60(c-src) - metabolism; Pyramidal cells; Rodents; Transgenes; Transgenic animals
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.9.4761

To examine the physiological role of the Fyn tyrosine kinase in neurons, we generated transgenic mice that expressed a fyn cDNA under the control of the calcium/calmodulin-dependent protein kinase IIα promoter. With this promoter, we detected only low expression of Fyn in the neonatal brain. In contrast, there was strong expression of the fyn-transgene in neurons of the adult forebrain. To determine whether the impairment of long-term potentiation (LTP) observed in adult fyn-deficient mice was caused directly by the lack of Fyn in adult hippocampal neurons or indirectly by an impairment in neuronal development, we generated fyn-rescue mice by introducing the wild-type fyn-transgene into mice carrying a targeted deletion in the endogenous fyn gene. In fyn-rescue mice, Schaffer collateral LTP was restored, even though the morphological abnormalities characteristic of fyn-deficient mice were still present. These results suggest that Fyn contributes, at least in part, to the molecular mechanisms of LTP induction.