Noboru Mizushima, Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Japan Macroautophagy (autophagy) requires more than 20 autophagy-related (ATG) genes, most of which are conserved in vertebrates. However, the common and distinct functions among the ATG genes remain unclear especially in vivo. Here we use zebrafish as a vertebrate model to investigate roles of ATG genes in vivo because it is easy to generate knockout animals and perform phenotypic analysis due to its transparency and external embryonic development. We have generated several ATG-deficient zebrafish lines and found that phenotypes of zebrafish lacking upstream and downstream ATG genes are different; zebrafish lacking upstream genes such as FIP200, ATG13, and ATG2a/b die ~10 days post fertilization (dpf), whereas those lacking downstream genes such as ATG5 and ATG16L1 die ~14 dpf. This is consistent to what we have observed in mice. We have also revealed a novel function of ATG genes in zebrafish, which is conserved in mice. These ATG-deficient zebrafish models are useful resources that can be used for comprehensive analysis of ATG genes in physiological and pathological settings in vivo.
This work was supported by JSPS KAKENHI Grants-in-Aid for Scientific Research on Innovative Areas (Grant Number 25111005) and JST ERATO (Grant Numbers JPMJER1702).
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