Fragile X Syndrome is the most common form of\ud
inherited mental retardation. It is also known for having\ud
a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always\ud
caused by inactivation of the X-linked FMR1 gene. A\ud
single knockout mouse model, fmr1-tm1Cgr, exists. In\ud
this report we further characterize the cognitive and\ud
behavioral phenotype of the fmr1-tm1Cgr Fragile X\ud
mouse through the use of F1 hybrid mice derived from\ud
two inbred strains (FVB/NJ and C57BL/6J). Use of F1\ud
hybrids allows focus on the effects of the fmr1-tm1Cgr\ud
allele with reduced influence from recessive alleles\ud
present in the parental inbred strains. We find that the\ud
cognitive phenotype of fmr1-tm1Cgr mice, including\ud
measures of working memory and learning set formation\ud
that are known to be seriously impacted in humans with\ud
Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any\ud
fmr1-tm1Cgr cognitive deficit is surprisingly mild or\ud
absent. There is, however, clear support presented for a\ud
robust audiogenic seizure phenotype in all strains tested,\ud
as well as increased entries into the center of an open\ud
field. Finally, a molecular examination of the fmr1-tm1Cgr\ud
mouse shows that, contrary to common belief, it is not a\ud
molecular null. Implications of this finding for interpretation of the phenotype are discussed.\u
