Neuroanatomy of the fragile X knockout mouse brain studied using in vivo high resolution magnetic resonance imaging

Abstract

Magnetic resonance imaging (MRI) of the brain of fragile X patients, the most frequent form of inherited mental retardation, has revealed abnormalities in the size of specific brain structures, including the cerebellar vermis, the hippocampus, and the ventricular system. We intended to quantify the differences observed in the patient studies in the fragile X knockout mouse model, which is a good model for the disease, paralleling the human disorder in having cognitive deficits, macro-orchidism, and immature dendritic spines. Therefore we set up MRI of the mouse brain which allowed us to measure the size of the brain structures reported to be abnormal in human fragile X patients in the mouse model. We did not find evidence for size alterations in various brain regions of the fragile X mouse model, but the method described may find a wide application in the study of mutant mouse models with neurological involvement.

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

“…Shortly, after the generation of the Fmr1 KO mouse in 1994 [80], the first MRI neuroanatomical assessment of the Fmr1 was performed [115]. Kooy et al [115] looked at the brains of 22 anesthetized mice in vivo (11 Fmr1 KO and 11 WT).…”

“…Shortly, after the generation of the Fmr1 KO mouse in 1994 [80], the first MRI neuroanatomical assessment of the Fmr1 was performed [115]. Kooy et al [115] looked at the brains of 22 anesthetized mice in vivo (11 Fmr1 KO and 11 WT). Images were acquired with high spatial resolution along the long axis of the mouse brain to assess the surface area of several different structures, including the total brain, cerebellum (anterior and posterior), fourth ventricle, subcortical gray matter, and hippocampus.…”

Craniofacial characteristics of fragile X syndrome in mouse and man

“…31 Early studies in the fragile X mouse found no brain volume changes. 32 However, another study showed significant volume decrease of the arbour vita of the cerebellum and more specifically of the deep cerebellar nuclei. Trends were found in the striatum (decrease) and the cerebral cortex of the parieto-temporal lobe (increase).…”

Brain studies of mouse models for neurogenetic disorders using in vivo magnetic resonance imaging (MRI)

“…However, no abnormalities were found in the brain structures of the knockout mice that were previously identified in humans. 17 …”

“…Longitudinal studies on one and the same animal have been performed, 7 and volumetric measurements of different parts of the brain are feasible. 11,17 In general, with the aid of a specific mouse brain atlas 18 the various brain regions are readily identified as the MRI images resemble the histological sections. However, on MRI the size and shape of the various components of the ventricular system differ markedly from histological views.…”