Zebrafish as a model animal for studying lysophosphatidic acid signaling

Junken Aoki, Hiroshi Yukiura

研究成果: Chapter

1 被引用数 (Scopus)

抄録

Lysophosphatidic acid (LPA) is a second-generation lysophospholipid mediator that exerts multiple biological functions through its own cognate receptors. LPA is produced by specific enzymatic reactions and activates receptors with similar structures (Edg receptors and P2Y receptors), which results in a variety of actions from embryonic blood vessel formation to development of cancer. LPArelated genes are highly conserved in vertebrates. In the zebrafish genome, three LPA-producing enzymes and nine LPA receptors are present. In vitro experiments have shown that LPA-related genes in zebrafish are conserved biochemically. LPArelated genes can be up- and downregulated by injecting morpholino antisense oligonucleotides (MOs) specific to LPA-related genes or mRNAs in zebrafish embryos. Such tools help to assess the biological function of these genes. For example, knockdown of the LPA-produced enzyme autotaxin (ATX) in zebrafish embryos resulted in malformation of embryonic blood vessel formation, which has also been observed in embryos from ATX-knockout mice. Simultaneous inactivation of multiple genes is possible by injecting more than one MO in zebrafish embryos, which makes it possible to identify the LPA receptors responsible for embryonic blood vessel formation. Gene functions can be also eliminated in zebrafish embryos by pharmacological tools such as enzyme inhibitors or receptor antagonists. Interestingly, overexpression of ATX in zebrafish embryos resulted in duplication of the heart (two-heart phenotype) and the phenotype was canceled by treating the embryos with LPA receptor antagonists. The zebrafish system is a powerful tool not only for identification of gene functions but also for development of drugsagainst enzymes and receptors.

本文言語English
ホスト出版物のタイトルBioactive Lipid Mediators
ホスト出版物のサブタイトルCurrent Reviews and Protocols
出版社Springer Japan
ページ199-206
ページ数8
ISBN(電子版)9784431556695
ISBN(印刷版)9784431556688
DOI
出版ステータスPublished - 2015 1 1

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)
  • 医学(全般)

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