Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons (Yoshii, Kuma et al.)
2016.10.10 Recent Publications
Saori R. Yoshii*, Akiko Kuma* (*equally contributed), Takumi Akashi, Taichi Hara, Atsushi Yamamoto, Yoshitaka Kurikawa, Eisuke Itakura, Satoshi Tsukamoto, Hiroshi Shitara, Yoshinobu Eishi, Noboru Mizushima.
Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons.
Dev Cell, 2016 Oct 10 DOI: 10.1016/j.devcel.2016.09.001
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.