W. Paradee et al., Fragile X mouse: Strain effects of knockout phenotype and evidence suggesting deficient amygdala function, NEUROSCIENC, 94(1), 1999, pp. 185-192
Fragile X syndrome is an X-linked form of mental retardation resulting from
the absence of expression of the fragile X mental retardation 1 gene. The
encoded protein is a ribosome-associated, RNA-binding protein thought to pl
ay a role in translational regulation of selective messenger RNA transcript
s. A knockout mouse has been described that exhibits subtle deficits in spa
tial learning but normal early-phase long-term potentiation. We expanded th
ese studies by examination of late-phase hippocampal long-term potentiation
, the protein synthesis-dependent form of long-term potentiation, in the Fm
r1 knockout mice. Here, late-phase long-term potentiation was normal, sugge
sting either that absence of fragile X mental retardation protein has no in
fluence on long-term potentiation or that any influence is too subtle to be
detected by this technique. Alternatively, the hippocampus may not be the
primary site affected by the absence of this protein. Accordingly, we exami
ned spatial learning in the knockout mice using the hippocampus-dependent M
orris water maze. Contrary to earlier reports, near-normal performance was
observed. Since the knockout line used in this study has been back-crossed
to C57BL/6 for more than 15 generations, whereas the line used in the earli
er studies contained a substantial strain 129 contribution, we examined F1
siblings of knockout and 129 crosses. Here, significant but subtle increase
d swim latencies in reversal trials were observed, in agreement with the pr
evious studies.
These data suggest strain differences between C57BL/6 and 129 that influenc
e the Fmr1 knockout phenotype. In order to investigate a paradigm less depe
ndent on hippocampal function, the knockout mice were examined using the co
nditional fear paradigm. Here, the knockout animals displayed significantly
less freezing behavior than their wild-type littermates following both con
textual and conditional fear stimuli. These data suggest that amygdala dist
urbances may also be involved in fragile X syndrome. (C) 1999 IBRO. Publish
ed by Elsevier Science Ltd.