Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome

Wiley - Tập 10 Số 1 - Trang 53-59 - 2004
Andrea Beckel‐Mitchener1, William T. Greenough2,1
1Neurotech, Beckman Institute, University of Illinois, Urbana, Illinois
2Departments of Psychology, Psychiatry, and Cell and Structural Biology, Neuroscience Program, University of Illinois, Urbana, Illinois

Tóm tắt

AbstractFragile X syndrome (FXS) is characterized by a pattern of morphological, functional, and molecular characteristics with, in at least some cases, apparent relationships among phenotypic features at different levels. Gross morphology differences in the sizes of some human brain regions are accompanied by fine structural alterations in the shapes and in the numbers of dendritic spines in both humans and the knockout mouse model. The excess number of spines, their immature appearance, and the impaired withdrawal of inappropriately oriented dendrites in FXS or the mouse model suggest impairment of neuronal maturation, including dendritic and spine pruning. It is not clear how these differences arise, although regionally or globally impaired translation of the mRNAs that interact with the Fmr1 protein product, FMRP, in the vicinity of the synapse, including genes involved in synapse development and plasticity and dendritic retraction, is certainly plausible. FMRP binds mRNA and may be involved in both transport and translation of the mRNAs it binds. The mRNAs it binds belong to multiple functional classes, apparently indicating that FMRP may impact multiple cellular processes. In one example, the glucocorticoid receptor, whose mRNA binds FMRP, regulates the stress‐sensitive glucocorticosteroids. Both human FXS and the mouse model exhibit a protracted elevation in glucocorticosteroids after stress. Possible relationships of other genes to morphological and functional characteristics of FXS are also discussed. MRDD Research Reviews 2004;10:53–59. © 2004 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1016/S0092-8674(03)00267-8

Bakker CE, 1994, Fmr1 knockout mice: A model to study fragile X mental retardation, Cell, 78, 23

10.1016/0165-0270(94)00125-Z

10.1111/j.1469-8749.2002.tb00277.x

10.1093/cercor/10.10.1045

10.1016/S0092-8674(01)00568-2

10.1016/S0306-4522(01)00036-7

10.1073/pnas.94.10.5401

10.1002/cne.901600202

10.1086/302260

10.1136/jmg.35.7.579

10.1177/002215540104901203

10.1016/S0006-8993(03)02363-1

10.1016/0165-3806(88)90160-5

10.1016/S0306-4530(01)00087-7

10.1002/ajmg.1320410306

10.1016/0301-0082(93)90002-A

10.1212/WNL.24.3.203

10.1016/0006-8993(79)90349-4

10.1016/S0387-7604(02)00102-X

10.1002/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B

10.1002/ajmg.10500

10.1002/hipo.10004

10.1016/S0925-4927(97)00019-X

10.1016/S0887-8994(96)00251-2

10.1038/sj.ejhg.5200348

10.1002/cne.901910102

10.1038/nature00850

10.1006/mcne.2000.0849

10.1016/0006-8993(72)90324-1

10.1073/pnas.96.22.12905

10.1002/hipo.10005

10.1016/S0896-6273(03)00034-5

10.1016/S0896-6273(02)00731-6

10.1111/j.1528-1157.1999.tb00824.x

10.1111/j.1528-1157.2000.tb01499.x

10.1523/JNEUROSCI.21-14-05139.2001

Purpura DP, 1979, Pathobiology of cortical neurons in metabolic and unclassified amentias, Res Publ Assoc Res Nerv Ment Dis, 57, 43

10.1016/S0166-2236(00)02118-4

10.1038/nm0295-159

10.1007/BF00687814

10.1053/seiz.2000.0492

10.1002/cne.902440302

10.1046/j.1528-1157.43.s.5.8.x

10.1006/bbrc.2000.3405

10.1016/S0896-6273(02)00748-1

10.1046/j.1528-1157.2001.042suppl.3008.x

10.1046/j.1460-9568.2000.00986.x

10.1073/pnas.94.10.5395

10.1002/(SICI)1097-4695(200005)43:2<159::AID-NEU6>3.0.CO;2-N

10.1097/00004703-200008000-00004

10.1002/ajmg.1320380267

10.1016/S0092-8674(03)00079-5

10.1017/S0952523800005599

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Wiley

Tập 10 Số 1

53-59

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