Elsevier

Neuroscience

Volume 76, Issue 2, January 1997, Pages 367-376
Neuroscience

Mildly impaired water maze performance in maleFmr1 knockout mice

https://doi.org/10.1016/S0306-4522(96)00224-2Get rights and content

Abstract

Fmr1 knockout mice constitute a putative model of fragile X syndrome, the most common form of heritable mental disability in humans. We have compared the performance of transgenic mice with anFmr1 knockout with that of normal littermates in hidden- and visible-platform water maze learning, and showed that knockouts exhibit subnormal spatial learning abilities and marginal motor performance deficits. During 12 training trials of the hidden-platform task, escape latency and path length decreased significantly in knockouts and control littermates, and no effect of genotype was found. During four ensuing reversal trials, however, significant differences were found between knockouts and control littermates both in escape latency and path length. During the visible-platform condition, the reversal trials also revealed a difference between knockouts and normal littermates in escape latency, but not in path length. Possibly due to marginal motor incapacity, knockouts swam significantly slower than controls during these latter trials. During both probe trials of the hidden-platform task, knockouts as well as normal littermates spent more time in the target quadrant than in the other quadrants, and percent of time spent in the target quadrant was the same in both groups; swimming velocity was not significantly different between knockouts and normal littermates during these trials. Entries in the target area during the probe trials did show a significant effect of genotype on number of entries.

The present results largely confirm and extend our previous findings. Impaired spatial abilities inFmr1 knockouts might have been due to relatively low response flexibility or high memory interference inFmr1 knockouts. It remains unclear, however, which brain region or neurochemical system might be involved in these disabilities. We conclude thatFmr1 knockout mice might be a valid model of fragile X mental retardation.

References (32)

  • VerkerkA.J.M.H. et al.

    Identification of a gene (FMR-1) containing a CGG repeat coincident with a fragile X breakpoint cluster region exhibiting length variation in fragile X syndrome

    Cell

    (1991)
  • WhishawI.Q. et al.

    Impairments in the acquisition, retention and selection of spatial navigation strategies after medial caudate-putamen lesions in rats

    Behav. Brain Res.

    (1987)
  • BakkerC.E. et al.

    Fmr1 knockout mice: a model to study fragile X mental retardation

    Cell

    (1994)
  • BrandeisR. et al.

    The use of the Morris water maze in the study of memory and learning

    Int. J. Neurosci.

    (1989)
  • EberhartD.E. et al.

    Identification of a cytoplasmic anchor domain responsible for the subcellular localization of the fragile X mental retardation protein, FMRP

    Am. J. Hum. Genet.

    (1995)
  • FreundL.S. et al.

    Cognitive profiles associated with the fra(X) syndrome in males and females

    Am. J Med. Genet.

    (1991)
  • Cited by (185)

    • Twenty years of discoveries emerging from mouse models of autism

      2023, Neuroscience and Biobehavioral Reviews
    View all citing articles on Scopus
    View full text