1 research outputs found
Knockout mouse model for Fxr2: a model for mental retardation
Fragile X syndrome is a common form of mental retardation caused by the
absence of the FMR1 protein, FMRP. Fmr1 knockout mice exhibit a phenotype
with some similarities to humans, such as macro-orchidism and behavioral
abnormalities. Two homologs of FMRP have been identified, FXR1P and FXR2P.
These proteins show high sequence similarity, including all functional
domains identified in FMRP, such as RNA binding domains. They have an
overlap in tissue distribution to that of FMRP. Interactions between the
three FXR proteins have also been described. FXR2P shows high expression
in brain and testis, like FMRP. To study the function of FXR2P, we
generated an Fxr2 knockout mouse model. No pathological differences
between knockout and wild-type mice were found in brain or testis. Given
the behavioral phenotype in fragile X patients and the phenotype
previously reported for the Fmr1 knockout mouse, we performed a thorough
evaluation of the Fxr2 knockout phenotype using a behavioral test battery.
Fxr2 knockout mice were hyperactive (i.e. traveled a greater distance,
spent more time moving and moved faster) in the open-field test, impaired
on the rotarod test, had reduced levels of prepulse inhibition, displayed
less contextual conditioned fear, impaired at locating the hidden platform
in the Morris water task and were less sensitive to a heat stimulus.
Interestingly, there are some behavioral phenotypes in Fxr2 knockout mice
which are similar to those observed in Fmr1 knockout mice, but there are
also some different behavioral abnormalities that are only observed in the
Fxr2 mutant mice. The findings implicate a role for Fxr2 in central
nervous system function