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

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

doi:10.1111/bpa.12758

Cited by 10 publications

(9 citation statements)

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“…18) The number of the in‰ammatory cells (monocytes and neutrophils) were increased in the brains of Ts1Cje embryos. 18) The increased number of in‰ammatory cells was improved in Ts1Cje-Erg mld2/＋/＋ mice. 18…”

Section: Impaired Neurogenesis and Enhanced Invasion Of In‰ammatorymentioning

confidence: 96%

ダウン症の胎生期脳発達遅滞における神経-血管相互作用異常の可能性

Ishihara

2021

YAKUGAKU ZASSHI

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Developmental retardation of the brain with reduced cortical neurogenesis is observed in Ts1Cje mice, a model of Down syndrome (DS) as it is in people with DS; however, the mechanisms and the responsible gene(s) remain unknown. The goal of the present study is to establish a therapeutic approach for treating the delayed brain development in DS. To achieve this, we have utilized multiple OMICS analyses, including proteomics and transcriptomics, to uncover the molecular alterations in the brains of DS model mice. Furthermore, we have elucidated that a transcriptional factor, the Erg gene, which is coded in the trisomic region, contributed to reduced cortical neurogenesis in the embryo of a DS mouse model by a molecular genetic technique, the``in vivo gene subtraction method''. In the current review, I will introduce our recent work, the identiˆcation of the gene responsible for delayed brain development in the DS mouse model and will discuss the possibility that blood vessel dysfunction may be associated with reduced embryonic neurogenesis in DS.

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Section: Impaired Neurogenesis and Enhanced Invasion Of In‰ammatorymentioning

confidence: 96%

ダウン症の胎生期脳発達遅滞における神経-血管相互作用異常の可能性

Ishihara

2021

YAKUGAKU ZASSHI

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“…These studies revealed that Rcan1 , Jam-b , Adamts1 , Erg , and Pttg1lp may be associated with the inhibition of tumor angiogenesis. In contrast to tumor angiogenesis, triplication of the Erg gene reduces cortical neurogenesis in the embryonic brains of DS model mice [ 42 ] ( Figure 1 ).…”

Section: Neurodevelopmental and Neuropsychiatric Disorders Associated...mentioning

confidence: 99%

Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases

Ishihara

Takata

Mizutani

2023

Life

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The vascular system of the prenatal brain is crucial for the development of the central nervous system. Communication between vessels and neural cells is bidirectional, and dysfunctional communication can lead to neurodevelopmental diseases. In the present review, we introduce neurodevelopmental and neuropsychiatric diseases potentially caused by disturbances in the neurovascular system and discuss candidate genes responsible for neurovascular system impairments. In contrast to diseases that can manifest during the developing stage, we have also summarized the disturbances of the neurovascular system in neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Furthermore, we discussed the role of abnormal vascularization and dysfunctional vessels in the development of neurovascular-related diseases.

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“…This may highlight a cause for immunodeficiency and myeloproliferative disorders that arise in DS. Ishihara et al, conducted a transcriptomic and flow cytometry analysis of E14.5 Ts1Cje mouse embryo brain, to allow a study of multiple genes and their impacts on the myeloproliferative system [56]. They found that neutrophil and monocyte ratios in CD45-positive haematopoietic cells increased, and macrophages decreased.…”

Section: Gene Expression Changes That Lead To Haematopoietic Cells/my...mentioning

confidence: 99%

Gene Expression Studies in Down Syndrome; What Do They Tell Us about Disease Phenotypes?

Chapman,

Ramnarine,

Zamke

et al. 2023

Preprint

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Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

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

Cited by 10 publications

References 58 publications

ダウン症の胎生期脳発達遅滞における神経-血管相互作用異常の可能性

ダウン症の胎生期脳発達遅滞における神経-血管相互作用異常の可能性

Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases

Gene Expression Studies in Down Syndrome; What Do They Tell Us about Disease Phenotypes?

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