Mice deficient in autophagy die either in utero (e.g., Beclin 1 and Fip200 knockout mice) [130] [131] [132] or within 24 hours after birth due, at least in part, to a deficiency in the mobilization of amino acids from various tissues (e.g., Atg3, Atg5, Atg7, Atg9, and Atg16L knockout mice) [49, [133] [134] [135] [136] . As a result, to investigate the physiological roles of autophagy, conditional knockout mice for Atg5, Atg7, or FIP200 and various tissue-specific Atg knockout mice have been established and analyzed [133, 137, 138] . For example, the liver-specific Atg7-deficient mouse displayed severe hepatomegaly accompanied by hepatocyte hypertrophy, resulting in severe liver injuries [133] . Mice lacking Atg5, Atg7, or FIP200 in the central nervous system exhibited behavioral deficits, such as abnormal limb-clasping reflexes and reduction of coordinated movement as well as massive neuronal loss in the cerebral and cerebellar cortices [137] [138] [139] . Loss of Atg5 in cardiac muscle caused cardiac hypertrophy, left ventricular dilatation, and systolic dysfunction [140] . Skeletal muscle-specific Atg5 or Atg7 knockout mice showed age-dependent muscle atrophy [141, 142] . Pancreatic β cell-specific Atg7 knockout animals exhibited degeneration of islets and impaired glucose tolerance with reduced insulin secretion [143, 144] . Podocytespecific deletion of Atg5 caused glomerulosclerosis in aging mice and these animals displayed increased susceptibility to proteinuric diseases caused by puromycin aminonucleoside and adriamycin [145] . Proximal tubule-specific Atg5 knockout mice were susceptible to ischemia-reperfusion injury [146] . Finally, deletion of Atg7 in bronchial epithelial cells resulted in hyperresponsiveness to cholinergic stimuli [147] . All together, these results undoubtedly indicate that basal autophagy prevents numerous life-threatening diseases.