Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 116-130 |
| Number of pages | 15 |
| Journal | Developmental Cell |
| Volume | 39 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2016 Oct 10 |
| Externally published | Yes |
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Keywords
- anemia
- Atg5
- autophagy
- hormone
- hypogonadism
- iron deficiency
- neonate
ASJC Scopus subject areas
- Developmental Biology
Cite this
Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons. / Yoshii, Saori R.; Kuma, Akiko; Akashi, Takumi; Hara, Taichi; Yamamoto, Atsushi; Kurikawa, Yoshitaka; Itakura, Eisuke; Tsukamoto, Satoshi; Shitara, Hiroshi; Eishi, Yoshinobu; Mizushima, Noboru.
In: Developmental Cell, Vol. 39, No. 1, 10.10.2016, p. 116-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Systemic Analysis of Atg5-Null Mice Rescued from Neonatal Lethality by Transgenic ATG5 Expression in Neurons
AU - Yoshii, Saori R.
AU - Kuma, Akiko
AU - Akashi, Takumi
AU - Hara, Taichi
AU - Yamamoto, Atsushi
AU - Kurikawa, Yoshitaka
AU - Itakura, Eisuke
AU - Tsukamoto, Satoshi
AU - Shitara, Hiroshi
AU - Eishi, Yoshinobu
AU - Mizushima, Noboru
PY - 2016/10/10
Y1 - 2016/10/10
N2 - 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.
AB - 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.
KW - anemia
KW - Atg5
KW - autophagy
KW - hormone
KW - hypogonadism
KW - iron deficiency
KW - neonate
UR - http://www.scopus.com/inward/record.url?scp=84992665477&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992665477&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2016.09.001
DO - 10.1016/j.devcel.2016.09.001
M3 - Article
C2 - 27693508
AN - SCOPUS:84992665477
VL - 39
SP - 116
EP - 130
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 1
ER -