Mammalian sialidase Neu1 is involved in various physiological functions, including cell adhesion, differentiation, cancer metastasis, and diabetes through lysosomal catabolism and desialylation of glycoproteins at the plasma membrane. Various animal models have been established to further explore the functions of vertebrate Neu1. The present study focused on zebrafish (Danio rerio) belonging to Cypriniformes as an experimental animal model with neu1 gene deficiency. The results revealed that the zebrafish Neu1 desialyzed both α2–3 and α2–6 sialic acid linkages from oligosaccharides and glycoproteins at pH 4.5, and it is highly conserved with other fish species and mammalian Neu1. Furthermore, Neu1-knockout zebrafish (Neu1-KO) was established through CRISPR/Cas9 genome editing. Neu1-KO fish exhibited slight abnormal embryogenesis with the accumulation of pleural effusion; however, no embryonic lethality was observed. Although Neu1-KO fish were able to be maintained as homozygous, they showed smaller body length and weight than the wild-type (WT) fish, and muscle atrophy and curvature of the vertebra were observed in adult Neu1-KO fish (8 months). The expression patterns of myod and myog transcription factors regulating muscle differentiation varied between Neu1-KO and WT fish embryo. Expression of lysosomal-related genes, including ctsa, lamp1a, and tfeb were up-regulated in adult Neu1-KO muscle as compared with WT. Furthermore, the expression pattern of genes involved in bone remodeling (runx2a, runx2b, and mmp9) was decreased in Neu1-KO fish. These phenotypes were quite similar to those of Neu1-KO mice and human sialidosis patients, indicating the effectiveness of the established Neu1-KO zebrafish for the study of vertebrate Neu1 sialidase.
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August 2020
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Cr(VI)-induced mitophagy contributes to mitochondrial loss, energy metabolism disorder, and cell death in L02 hepatocytes. The fluorescent image shows hepatocytes containing autophagosomes. For more information, see the article by Zhang and colleagues (pp. 2607–2619). The image was provided by Fang Xiao.
Research Article|
August 12 2020
Establishment and characterization of Neu1-knockout zebrafish and its abnormal clinical phenotypes
Keiji Okada;
Keiji Okada
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
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Ryo Takase;
Ryo Takase
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
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Yurie Hamaoka;
Yurie Hamaoka
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
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Akinobu Honda;
Akinobu Honda
2The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
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Asami Ikeda;
Asami Ikeda
2The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
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Yoichiro Hokazono;
Yoichiro Hokazono
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
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Yutaro Maeda;
Yutaro Maeda
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
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Oki Hayasaka;
Oki Hayasaka
2The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
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Tomonari Kotani;
Tomonari Kotani
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
2The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
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Masaharu Komatsu;
Masaharu Komatsu
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
2The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
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Kazuhiro Shiozaki
1Faculty of Fisheries, Kagoshima University, Kagoshima, Japan
2The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
Correspondence: Kazuhiro Shiozaki (shiozaki@fish.kagoshima-u.ac.jp)
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Publisher: Portland Press Ltd
Received:
April 30 2020
Revision Received:
July 09 2020
Accepted:
July 17 2020
Accepted Manuscript online:
July 20 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (15): 2841–2857.
Article history
Received:
April 30 2020
Revision Received:
July 09 2020
Accepted:
July 17 2020
Accepted Manuscript online:
July 20 2020
Citation
Keiji Okada, Ryo Takase, Yurie Hamaoka, Akinobu Honda, Asami Ikeda, Yoichiro Hokazono, Yutaro Maeda, Oki Hayasaka, Tomonari Kotani, Masaharu Komatsu, Kazuhiro Shiozaki; Establishment and characterization of Neu1-knockout zebrafish and its abnormal clinical phenotypes. Biochem J 14 August 2020; 477 (15): 2841–2857. doi: https://doi.org/10.1042/BCJ20200348
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