Anatomical phenotyping in a mouse model of fragile X syndrome with magnetic resonance imaging.

Fragile X Syndrome (FXS) is the most common single gene cause of inherited mental impairment, and cognitive deficits can range from simple learning disabilities to mental retardation. Human FXS is caused by a loss of the Fragile X Mental Retardation Protein (FMRP). The fragile X knockout (FX KO) mouse also shows a loss of FMRP, as well as many of the physical and behavioural characteristics of human FXS. This work aims to characterize the anatomical changes between the FX KO and a corresponding wild type mouse. Significant volume decreases were found in two regions within the deep cerebellar nuclei, namely the nucleus interpositus and the fastigial nucleus, which may be caused by a loss of neurons as indicated by histological analysis. Well-known links between these nuclei and previously established behavioural and physical characteristics of FXS are discussed. The loss of FMRP has a significant effect on these two nuclei, and future studies of FXS should evaluate the biochemical, physiological, and behavioral consequences of alterations in these key nuclei. Copyright 2010 Elsevier Inc. All rights reserved.