Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/61819
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Type: | Journal article |
Title: | Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down Syndrome |
Author: | Hewitt, C. Ling, K. Merson, T. Simpson, K. Ritchie, M. King, S. Pritchard, M. Smyth, G. Thomas, T. Scott, H. Voss, A. |
Citation: | PLoS One, 2010; 5(7):1-15 |
Publisher: | Public Library of Science |
Issue Date: | 2010 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Aziz, S.A. |
Statement of Responsibility: | Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Voss |
Abstract: | Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals. |
Keywords: | Neurons Cells, Cultured Stem Cells Animals Mice, Inbred C57BL Mice Down Syndrome Disease Models, Animal Trisomy Protein-Serine-Threonine Kinases Cell Cycle Proteins DNA-Binding Proteins BRCA2 Protein Nuclear Proteins Fluorescent Antibody Technique Oligonucleotide Array Sequence Analysis Immunohistochemistry Reverse Transcriptase Polymerase Chain Reaction Apoptosis Cell Differentiation Cell Movement Female Male Gene Regulatory Networks Neurogenesis Aurora Kinase A Aurora Kinases Minichromosome Maintenance Complex Component 7 |
Rights: | © 2010 Hewitt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0011561 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/171601 http://purl.org/au-research/grants/nhmrc/461204 http://purl.org/au-research/grants/nhmrc/575512 http://purl.org/au-research/grants/nhmrc/219176 http://purl.org/au-research/grants/nhmrc/257501 http://purl.org/au-research/grants/nhmrc/257529 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0011561 |
Appears in Collections: | Aurora harvest Medicine publications |
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hdl_61819.pdf | 2.81 MB | Adobe PDF | View/Open |
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