Altered maturation of the primary somatosensory cortex in a mouse model of fragile X syndrome.

Details

Serval ID
serval:BIB_4A309A77A1F8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Altered maturation of the primary somatosensory cortex in a mouse model of fragile X syndrome.
Journal
Human molecular genetics
Author(s)
Till S.M., Wijetunge L.S., Seidel V.G., Harlow E., Wright A.K., Bagni C., Contractor A., Gillingwater T.H., Kind P.C.
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
15/05/2012
Volume
21
Number
10
Pages
2143-2156
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and results from the loss of the fragile X mental retardation protein (FMRP). Many fragile X-related cognitive and behavioral features emerge during childhood and are associated with abnormal synaptic and cellular organization of the cerebral cortex. Identifying the roles of FMRP in cortical development will provide a basis for understanding the pathogenesis of the syndrome. However, how the loss of FMRP influences the developmental trajectory of cortical maturation remains unclear. We took advantage of the stereotyped and well-characterized development of the murine primary somatosensory cortex to examine cortical maturation during a time-window that corresponds to late embryonic and early postnatal development in the human. In the Fmr1 knockout mouse, we find a delay in somatosensory map formation, alterations in the morphology profile of dendrites and spines of layer 4 neurons and a decrease in the synaptic levels of proteins involved in glutamate receptor signaling at times corresponding to the highest levels of FMRP expression. In contrast, cortical arealization, synaptic density in layer 4 and early postnatal regulation of mRNAs encoding synaptic proteins are not altered in Fmr1 knockout mice. The specificity of the developmental delay in Fmr1 knockout mice indicates that the loss of FMRP does not result in a general stalling of cerebral cortex maturation. Instead, our results suggest that inaccurate timing of developmental processes caused by the loss of FMRP may lead to alterations in neural circuitry that underlie behavioral and cognitive dysfunctions associated with FXS.

Keywords
Animals, Disease Models, Animal, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/metabolism, Mice, Mice, Knockout, Microscopy, Electron, RNA, Messenger/metabolism, Somatosensory Cortex/metabolism
Pubmed
Open Access
Yes
Create date
06/03/2017 17:23
Last modification date
20/08/2019 13:57
Usage data