Journal article

Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

Keiichi Ishihara, Ryohei Shimizu, Kazuyuki Takata, Eri Kawashita, Kenji Amano, Atsushi Shimohata, Donovan Low, Takeshi Nabe, Haruhiko Sago, Warren S Alexander, Florent Ginhoux, Kazuhiro Yamakawa, Satoshi Akiba

BRAIN PATHOLOGY | WILEY | Published : 2020

Abstract

Some mouse models of Down syndrome (DS), including Ts1Cje mice, exhibit impaired prenatal neurogenesis with yet unknown molecular mechanism. To gain insights into the impaired neurogenesis, a transcriptomic and flow cytometry analysis of E14.5 Ts1Cje embryo brain was performed. Our analysis revealed that the neutrophil and monocyte ratios in the CD45-positive hematopoietic cells were relatively increased, in agreement with the altered expression of inflammation/immune-related genes, in Ts1Cje embryonic brain, whereas the relative number of brain macrophages was decreased in comparison to wild-type mice. Similar upregulation of inflammation-associated mRNAs was observed in other DS mouse mode..

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University of Melbourne Researchers

Grants

Awarded by JSPS KAKENHI


Awarded by Kyoto Pharmaceutical University Fund for the Promotion of Scientific Research


Awarded by Singapore National Research Foundation Senior Investigatorship (NRFI)


Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

We are grateful to F. Tsushimi, S. Sugimoto, A. Izumoto, S. Wakigi, A. Nakano, (Dept. of Pathol. Biochem.) and K. Kaneda (Dept. of Clin. Transl. Physiol.) at Kyoto Pharmaceutical University for assistance in the bioinfomatics analysis and immunohistochemistry. We are also thankful for the help of S. Mifsud, The Walter and Eliza Hall Institute of Medical Research for transporting the Erg<SUP>Mld2/+</SUP> mice. F.G. is an EMBO YIP awardee.This study was supported in part by grants from Takeda Science Foundation (2016) (to K.I.), the JSPS KAKENHI Grant Numbers 18K06940 (to K.I.), the Vehicle Racing Commemorative Foundation (2017) (to K.I.), Kyoto Pharmaceutical University Fund for the Promotion of Scientific Research (to K.I.), Fellowship (1058344) and Program Grant (1113577) from the Australian National Health and Medical Research Council (to W.A.) and Singapore Immunology Network (SIgN) core funding as well as a Singapore National Research Foundation Senior Investigatorship (NRFI) NRF2016NRF-NRFI001-02 (to F.G.).