Atg7 deletion in various tissues
To investigate the physiological roles of autophagy in mice, conditional knockout mice for an autophagy-essential gene, Atg7, were generated. A number of groups have generated various tissue-specific autophagy-deficient mice. Many of the molecular mechanisms underpinning autophagy and the physiologic roles of these processes have since been elucidated.
Autophagy is a pathway for bulk protein degradation that has been conserved in most eukaryotic cells. The initial steps of autophagy include the formation and elongation of the isolation membrane. This membrane enwraps organelles and other cytoplasmic components until forming a double-membrane vesicle called an autophagosome. The biogenesis of autophagosomes requires proteins encoded by autophagy-related (Atg) genes, most of which were initially identified in yeast. To date, Atg5 conditional knockout mice, GFP-tagged Map1lc3a Tg mice (mammalian homologue of Atg8p), and other various Atg-deficient mice have been established .
While autophagy has been considered a non-selective process, growing evidence indicates that selectivity of autophagy plays an important role in the turnover of aberrant proteins, disposal of damaged organelles, and elimination of protein aggregates and invading pathogens. Tissue-specific Atg7-deficient mice exhibit liver injury, diabetes, muscle atrophy, and neurodegeneration [2–4]. Conventional and conditional Atg7 knockout mice provide the opportunity to understand the role of autophagy in homeostasis and various common diseases.
Related strain : B6;B6CB-Atg3tm1/TchiRbrc RBRC02761
|Depositor||:||Dr. Masaaki Komatsu
Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Scienceo
|References||:||||Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell; 147(4):728-41, 2011.|
|||Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, Kominami E, Tanaka K, Chiba T. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J Cell Biol; 169(3):425-34, 2005.|
|||Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature; 441(7095):880-4, 2006.|
|||Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M. Autophagy is required to maintain muscle mass. Cell Metab; 10(6):507-15, 2009.|