Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons.
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.
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Saori R
SR
Yoshii
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Japan Science and Technology Agency, PRESTO, Saitama 332-0012, Japan.
Akiko
A
Kuma
Department of Human Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Takumi
T
Akashi
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Taichi
T
Hara
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Comprehensive Reproductive Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Atsushi
A
Yamamoto
Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Yoshitaka
Y
Kurikawa
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Eisuke
E
Itakura
Laboratory Animal and Genome Sciences Section, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
Satoshi
S
Tsukamoto
Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Hiroshi
H
Shitara
Department of Human Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Yoshinobu
Y
Eishi
Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: nmizu@m.u-tokyo.ac.jp.
Noboru
N
Mizushima
D000740:Anemia / Q000235:genetics / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D000071187:Autophagy-Related Protein 5 / Q000172:deficiency* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006062:Gonadotropins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013091:Spermatogenesis; D013739:Testosterone / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D006062:Gonadotropins; D057149:Ubiquitinated Proteins; D049452:Green Fluorescent Proteins; D013739:Testosterone; D007501:Iron; D010751:Phosphopyruvate Hydratase
Atg5; anemia; autophagy; hormone; hypogonadism; iron deficiency; neonate