Delayed Development of Dendritic Spines in Fxr2 Knockout Mouse

Abstract

Fragile X syndrome, the most common form of inherited mental retardation is caused by silencing of the Fmr1 (fragile x mental retardation-1) gene. Two mammalian homologues of Fmr1 have been identified: fragile X-related Pro- tein 1 (Fxr1) and Protein 2Fxr2. Aberrations in dendritic spines of Fragile X syndrome patients and Fmr1 null mice im- plicate FMRP in synapse fo rmation and function. However, no structural analysis has been performed on Fxr2 null mice. Here we examined dendritic spines in brains of Fxr2 KO mouse. We report that at the age of 2 weeks, unlike in the Fmr1 null mice, spines in the somatosensory cortex and the hippocampus of Fxr2 null mice are less dense compared to wild type mice. On the other hand, there is an increase in spine length similar to that reported in the Fmr1 null mice. These dif- ferences in spine density and morphology are no longer detected by the age of 4 weeks. Our results indicate for the first time that Fxr2 plays a role in spine development and further suggest that Fxr2 has only partially overlapping function with Fmr1.