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Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome


Hewitt, Chelsee Ann and Ling, King Hwa and Merson, Tobias D. and Simpson, Ken M. and Ritchie, Matthew E. and King, Sarah L. and Pritchard, Melanie A. and Smyth, Gordon K. and Thomas, Tim and Scott, Hamish S. and Voss, Anne K. (2010) Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome. PLOS ONE, 5 (7). art. no. e11561. pp. 1-15. ISSN 1932-6203


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.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Medicine and Health Science
DOI Number: https://doi.org/10.1371/journal.pone.0011561
Publisher: Public Library of Science
Keywords: Down syndrome; Ts1Cje; Neurogenesis defects; Gene expression networks; Gene regulatory networks
Depositing User: Raja Norazlinda Raja Azenam
Date Deposited: 18 Oct 2013 02:26
Last Modified: 01 Oct 2019 04:23
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1371/journal.pone.0011561
URI: http://psasir.upm.edu.my/id/eprint/14865
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