Document Detail

A yeast model of Down syndrome.
MedLine Citation:
PMID:  18023319     Owner:  NLM     Status:  MEDLINE    
The recent discovery that cellular proliferation was reduced in aneuploid haploid yeast supports a long-standing argument that the developmental neurophenotype of Down syndrome is not uniquely a result of the effects of increased gene dosage. Instead, some phenotypic outcomes appear to resemble those caused by disrupted cellular homeostasis induced by aneuploidy. Decreased cellular proliferation has been identified in the cerebellum and hippocampus of Down syndrome mouse models and in the post-mortem hippocampus and germinal matrix of Down syndrome fetuses. Consistent with predominantly stochastic gene expression and increased energy demands induced by aneuploidy, the "buffering" canalization processes in Down syndrome would be reduced thereby giving rise to increased variance to less stable developmental pathways such as proliferation. The nature and extent of phenotypes due to reduced canalization would depend on the tissue; which is also a question for future research to address. A conceptual model is presented here to demonstrate the nature of influences affecting phenotypes. Ultimately, in Down syndrome, exigent periods of neurodevelopment increasingly appear to reflect the burden of disrupted homeostasis.
Randal X Moldrich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2007-10-06
Journal Detail:
Title:  International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience     Volume:  25     ISSN:  0736-5748     ISO Abbreviation:  Int. J. Dev. Neurosci.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-07     Completed Date:  2008-02-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8401784     Medline TA:  Int J Dev Neurosci     Country:  England    
Other Details:
Languages:  eng     Pagination:  539-43     Citation Subset:  IM    
The Queensland Brain Institute, The University of Queensland, St. Lucia, Queensland 4072, Australia.
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MeSH Terms
Cell Proliferation
Down Syndrome / genetics*,  pathology
Gene Dosage
Yeasts / genetics*

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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