Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons

Publication date: Available online 29 September 2016
Source:Developmental Cell
Author(s): Saori R. Yoshii, Akiko Kuma, Takumi Akashi, Taichi Hara, Atsushi Yamamoto, Yoshitaka Kurikawa, Eisuke Itakura, Satoshi Tsukamoto, Hiroshi Shitara, Yoshinobu Eishi, Noboru Mizushima
Autophagy is a cytoplasmic degradation system that is important for starvation adaptation and cellular quality control. Previously, we reported that Atg5-null mice are neonatal lethal; however, the exact cause of their death remains unknown. Here, we show that restoration of ATG5 in the brain is sufficient to rescue Atg5-null mice from neonatal lethality. This suggests that neuronal dysfunction, including suckling failure, is the primary cause of the death of Atg5-null neonates, which would further be accelerated by nutrient insufficiency due to a systemic failure in autophagy. The rescued Atg5-null mouse model, as a resource, allows us to investigate the physiological roles of autophagy in the whole body after the neonatal period. These rescued mice demonstrate previously unappreciated abnormalities such as hypogonadism and iron-deficiency anemia. These observations provide new insights into the physiological roles of the autophagy factor ATG5.

Graphical abstract

Teaser

Loss of the key autophagy factor Atg5 causes neonatal lethality. Yoshii, Kuma et al. show that neuron-specific transgenic expression of ATG5 can rescue lethality, suggesting that neuronal dysfunction is the primary cause of lethality. Rescued mice develop multiple abnormalities and provide a resource for dissection of physiological roles of autophagy.


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