Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene.
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 IIalpha 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.
Kojima
N
N
Laboratory of Neurochemistry, National Institute for Physiological Sciences, Okazaki 444, Japan.
Wang
J
J
Mansuy
I M
IM
Grant
S G
SG
Mayford
M
M
Kandel
E R
ER
D000367:Age Factors; D000818:Animals; D006624:Hippocampus / Q000002:abnormalities / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency*; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D051076:Proto-Oncogene Proteins c-fyn; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D016392:Proto-Oncogene Proteins pp60(c-src)