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Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

Background: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication o...

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Main Authors: Ling, King Hwa, Hewitt, Chelsee Ann, Tan, Kai Leng, Cheah, Pike See, Vidyadaran, Sharmili, Lai, Mei I., Lee, Han Chung, Simpson, Ken, Hyde, Lavinia, Pritchard, Melanie A., Smyth, Gordon K., Thomas, Tim, Scott, Hamish S.
Format: Article
Language:English
Published: BioMed Central 2014
Online Access:http://psasir.upm.edu.my/id/eprint/37726/1/Functional%20transcriptome%20analysis%20of%20the%20postnatal%20brain%20of%20the%20Ts1Cje%20mouse%20model%20for%20Down%20syndrome%20reveals%20global%20disruption%20of%20interferon.pdf
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spelling oai:psasir.upm.edu.my:37726 http://psasir.upm.edu.my/id/eprint/37726/ Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks Ling, King Hwa Hewitt, Chelsee Ann Tan, Kai Leng Cheah, Pike See Vidyadaran, Sharmili Lai, Mei I. Lee, Han Chung Simpson, Ken Hyde, Lavinia Pritchard, Melanie A. Smyth, Gordon K. Thomas, Tim Scott, Hamish S. Background: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84. Results: Gene expression profiling identified a total of 317 differentially expressed genes (DEGs), selected from various spatiotemporal comparisons, between Ts1Cje and disomic mice. A total of 201 DEGs were identified from the cerebellum, 129 from the hippocampus and 40 from the cerebral cortex. Of these, only 18 DEGs were identified as common to all three brain regions and 15 were located in the triplicated segment. We validated 8 selected DEGs from the cerebral cortex (Brwd1, Donson, Erdr1, Ifnar1, Itgb8, Itsn1, Mrps6 and Tmem50b), 18 DEGs from the cerebellum (Atp5o, Brwd1, Donson, Dopey2, Erdr1, Hmgn1, Ifnar1, Ifnar2, Ifngr2, Itgb8, Itsn1, Mrps6, Paxbp1, Son, Stat1, Tbata, Tmem50b and Wrb) and 11 DEGs from the hippocampus (Atp5o, Brwd1, Cbr1, Donson, Erdr1, Itgb8, Itsn1, Morc3, Son, Tmem50b and Wrb). Functional clustering analysis of the 317 DEGs identified interferon-related signal transduction as the most significantly dysregulated pathway in Ts1Cje postnatal brain development. RT-qPCR and western blotting analysis showed both Ifnar1 and Stat1 were over-expressed in P84 Ts1Cje cerebral cortex and cerebellum as compared to wild type littermates. Conclusions: These findings suggest over-expression of interferon receptor may lead to over-stimulation of Jak-Stat signaling pathway which may contribute to the neuropathology in Ts1Cje or DS brain. The role of interferon mediated activation or inhibition of signal transduction including Jak-Stat signaling pathway has been well characterized in various biological processes and disease models including DS but information pertaining to the role of this pathway in the development and function of the Ts1Cje or DS brain remains scarce and warrants further investigation. BioMed Central 2014 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/37726/1/Functional%20transcriptome%20analysis%20of%20the%20postnatal%20brain%20of%20the%20Ts1Cje%20mouse%20model%20for%20Down%20syndrome%20reveals%20global%20disruption%20of%20interferon.pdf Ling, King Hwa and Hewitt, Chelsee Ann and Tan, Kai Leng and Cheah, Pike See and Vidyadaran, Sharmili and Lai, Mei I. and Lee, Han Chung and Simpson, Ken and Hyde, Lavinia and Pritchard, Melanie A. and Smyth, Gordon K. and Thomas, Tim and Scott, Hamish S. (2014) Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks. BMC Genomics, 15. art. no. 624. pp. 1-19. ISSN 1471-2164 10.1186/1471-2164-15-624
institution UPM IR
collection UPM IR
language English
description Background: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84. Results: Gene expression profiling identified a total of 317 differentially expressed genes (DEGs), selected from various spatiotemporal comparisons, between Ts1Cje and disomic mice. A total of 201 DEGs were identified from the cerebellum, 129 from the hippocampus and 40 from the cerebral cortex. Of these, only 18 DEGs were identified as common to all three brain regions and 15 were located in the triplicated segment. We validated 8 selected DEGs from the cerebral cortex (Brwd1, Donson, Erdr1, Ifnar1, Itgb8, Itsn1, Mrps6 and Tmem50b), 18 DEGs from the cerebellum (Atp5o, Brwd1, Donson, Dopey2, Erdr1, Hmgn1, Ifnar1, Ifnar2, Ifngr2, Itgb8, Itsn1, Mrps6, Paxbp1, Son, Stat1, Tbata, Tmem50b and Wrb) and 11 DEGs from the hippocampus (Atp5o, Brwd1, Cbr1, Donson, Erdr1, Itgb8, Itsn1, Morc3, Son, Tmem50b and Wrb). Functional clustering analysis of the 317 DEGs identified interferon-related signal transduction as the most significantly dysregulated pathway in Ts1Cje postnatal brain development. RT-qPCR and western blotting analysis showed both Ifnar1 and Stat1 were over-expressed in P84 Ts1Cje cerebral cortex and cerebellum as compared to wild type littermates. Conclusions: These findings suggest over-expression of interferon receptor may lead to over-stimulation of Jak-Stat signaling pathway which may contribute to the neuropathology in Ts1Cje or DS brain. The role of interferon mediated activation or inhibition of signal transduction including Jak-Stat signaling pathway has been well characterized in various biological processes and disease models including DS but information pertaining to the role of this pathway in the development and function of the Ts1Cje or DS brain remains scarce and warrants further investigation.
format Article
author Ling, King Hwa
Hewitt, Chelsee Ann
Tan, Kai Leng
Cheah, Pike See
Vidyadaran, Sharmili
Lai, Mei I.
Lee, Han Chung
Simpson, Ken
Hyde, Lavinia
Pritchard, Melanie A.
Smyth, Gordon K.
Thomas, Tim
Scott, Hamish S.
spellingShingle Ling, King Hwa
Hewitt, Chelsee Ann
Tan, Kai Leng
Cheah, Pike See
Vidyadaran, Sharmili
Lai, Mei I.
Lee, Han Chung
Simpson, Ken
Hyde, Lavinia
Pritchard, Melanie A.
Smyth, Gordon K.
Thomas, Tim
Scott, Hamish S.
Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks
author_facet Ling, King Hwa
Hewitt, Chelsee Ann
Tan, Kai Leng
Cheah, Pike See
Vidyadaran, Sharmili
Lai, Mei I.
Lee, Han Chung
Simpson, Ken
Hyde, Lavinia
Pritchard, Melanie A.
Smyth, Gordon K.
Thomas, Tim
Scott, Hamish S.
author_sort Ling, King Hwa
title Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks
title_short Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks
title_full Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks
title_fullStr Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks
title_full_unstemmed Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks
title_sort functional transcriptome analysis of the postnatal brain of the ts1cje mouse model for down syndrome reveals global disruption of interferon-related molecular networks
publisher BioMed Central
publishDate 2014
url http://psasir.upm.edu.my/id/eprint/37726/1/Functional%20transcriptome%20analysis%20of%20the%20postnatal%20brain%20of%20the%20Ts1Cje%20mouse%20model%20for%20Down%20syndrome%20reveals%20global%20disruption%20of%20interferon.pdf
_version_ 1782721301040857088
score 12.935284

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