Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function
Section snippets
Subjects
Fmr1 knockout mice, from a colony founded by Fmr1 knockout animals3 kindly provided by Drs B. Oostra and P. Willems, were used. This colony had been bred to become congenic on the C57BL/6 background and at the time of this study was at least 15 generations against C57BL/6. Female heterozygous Fmr1 knockout mice3 were bred with either wild-type C57BL/6 or 129Re/J males. Only male knockout mice and their normal X chromosome male littermates were used. Knockouts and their control littermates were
Electrophysiology
Since Fmrp associates with ribosomes and may be involved in protein synthesis,2., 8., 10., 22., 48. we studied L-LTP in the Fmr1 knockout mouse, which is dependent on both protein and RNA synthesis.1., 12., 13., 14., 35., 38. In agreement with previous early LTP studies by Godfraind et al.,15 hippocampal LTP at the Schaffer collateral–CA1 synapse showed no difference in evoked responses at 120 min post-tetanus between knockout animals and their control littermates [Fig. 1; 194.7±30% (n=6) for
Electrophysiology
The studies described above expand our understanding of the mouse model for fragile X syndrome. Despite an association of Fmrp with ribosomes,10., 11., 48. no effects were observed on late phase, protein synthesis-dependent, hippocampal LTP. Although L-LTP requires intact translation,12., 38. the absence of Fmrp had no demonstrable effect on L-LTP in the knockout animals. Since fragile X patients demonstrate visual–spatial and short-term memory deficits,4., 30. and the knockout mice were
Acknowledgements
This work was supported, in part, by grants R37 HD20521 and PO1 HD35576 to S.T.W.; S.T.W. is an investigator and W.P. and H.E.M. are associates of the Howard Hughes Medical Institute.
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