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Allele Symbol Allele Name Allele ID |
Atg5tm1Myok targeted mutation 1, Minesuke Yokoyama MGI:3663625 |
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| Summary |
20 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice appear normal at weaning but fail to gain weight
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• increase in levels of circulating neutrophils
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• increase in levels of circulating lymphocytes
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• increase in levels of circulating monocytes
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• IgG deposition in the glomeruli of kidneys
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• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
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• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
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• in 52-week old mice
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• in 52-week old mice
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• in 52-week old mice
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• in 52-week old mice
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• increase in levels of circulating neutrophils
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• increase in levels of circulating lymphocytes
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• increase in levels of circulating monocytes
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• IgG deposition in the glomeruli of kidneys
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• macrophages exhibit an acute elevation of proinflammatory cytokines IL-1beta, IL-6, and IP-10, but not IL-10, in response to ingesting dying cells that is not seen in control macrophages
• however, neither bone marrow-derived macrophages nor peritoneal exudate macrophages from 52 week old mice show any defects in the engulfment of dying cells in vitro indicating normal phagocytic capacity
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• levels of CXCL1, CCL4 and CCL2 are increased in 52-week old mice
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• in 52-week old mice
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• in 52-week old mice
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• in 52-week old mice
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• in 52-week old mice
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• mice develop a systemic lupus erythematosus-like disease (SLE)
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• increase in serum levels of a broad array of antibodies against autoantigens commonly associated with SLE
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• kidneys from aged mice show endocapillary proliferative glomerulonephritis
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• mice show indications of kidney damage and show increased functional markers of kidney injury
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• IgG and complement C1q deposition in the glomeruli of kidneys
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• kidneys from aged mice show endocapillary proliferative glomerulonephritis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:235399 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• impaired autophagosome formation
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• impaired autophagosome formation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice die after thoracic transverse aortic constriction of heart failure
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• 1 week following thoracic transverse aortic constriction (TAC) or a 7 day treatment with isoproterenol left ventricular dilation is observed
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• thoracic transverse aortic constriction (TAC) and isoproterenol induce severe cardiac dysfunction
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• 4 weeks following TAC
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• following a 7 day treatment with isoproterenol the left ventricle is dilated and mice exhibit severe cardiac dysfuction, unlike wild-type mice where the treatment has no significant effect
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• diffuse cytoplasmic signals and inclusions are found in the liver
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• few inclusions form immediately following injection of inosinic acid-polycytidylic acid (pIpC) but large ubiquitin-positive inclusions are present 16 days post-injection
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, (left) kidney weight-to-body weight is slight increased relative to littermate controls
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• increased excretion of most amino acids, with significant increases in threonine, tryptophan, valine, and alanine excretion is observed in 6-month old mice
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• mice exhibit mild glycosuria at 6 months of age
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• at 8 weeks, slight tubular cell hypertrophy is observed but interstitial nephritis or fibrosis is not apparent; accumulation of numerous crescent membranous structures in tubular epithelial cells, primarily adjacent to mitochondria is present at 6 weeks with accumulation of similar (smaller) structures observed at 9 months
• deformed mitochondria are found in tubular cells of mutants but not in controls
• accumulation of cytosolic amorphous substrates in proximal tubular cells is apparent at 6 months
• massive accumulation of p62- and ubiquitin-positive inclusion bodies is observed almost exclusively in proximal tubules at 9 months
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| N |
• all mice survive during observational period (<9 months)
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| N |
• no albuminuria or increased blood urea nitrogen level is observed in mice up to 9 months of age compared to littermate controls
• no phosphaturia is observed
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• in kidney cortex homogenates from 8-week old mice, conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II is suppressed, indicative of defective autophagy
• after ischemia-reperfusion injury, severely injured tubules with accumulation of tubular sediments and vacuolation in the cortex are observed, whereas injury severity is reduced in injured controls; conversion of LC-I to LC-II in cortex as measured by Western blot is significantly suppressed indicating autophagy deficiency
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• increased excretion of most amino acids, with significant increases in threonine, tryptophan, valine, and alanine excretion is observed in 6-month old mice
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• mice exhibit mild glycosuria at 6 months of age
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• in kidney cortex homogenates from 8-week old mice, conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II is suppressed, indicative of defective autophagy
• after ischemia-reperfusion injury, severely injured tubules with accumulation of tubular sediments and vacuolation in the cortex are observed, whereas injury severity is reduced in injured controls; conversion of LC-I to LC-II in cortex as measured by Western blot is significantly suppressed indicating autophagy deficiency
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• at 8 weeks of age, (left) kidney weight-to-body weight is slight increased relative to littermate controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Cataract development in Atg5tm1Myok/Atg5tm1Myok Tg(CAG-EGFP/Map1lc3b)53Nmz/0 Tg(Cryaa-cre)10Mlr/0 mice
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• absent in lens fiber cells
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• absent autophagy in lens fiber cells
• disorganized in the cortical region of aged mice
• however, organelle degradation is normal
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• by 6 to 9 months that develops progressively with age
• severe, bilateral at 21 months
• with accumulation of insoluble oxidized proteins and crystallins
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• absent in lens fiber cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• complete loss of autophagy in hypothalamus neurons whether mice are fed a normal or high-fat diet
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| N |
• mice fed a normal diet exhibit normal fat mass and adiposity
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| N |
• mice fed standard chow exhibit normal body weight, lean mass and body length
• mice fed a high-fat diet exhibit normal body weight gain
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| N |
• mice exhibit normal POMC neuron numbers and corticotroph function
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• complete loss of autophagy in hypothalamus neurons whether mice are fed a normal or high-fat diet
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at 12 weeks of age, ERG responses are not different from wild-type littermate controls
• no significant loss of nuclei in the outer nuclear layer by 24 weeks through 1.5 years of age
• when control and mutant mice received an i.p. injection of 9-cis retinal and then were dark-adapted for 24 hours, scotopic and photopic electroretinogram recordings showed no significant differences in rod and cone function
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• rod responses to bright-light stimuli are decreased at 16 weeks compared to controls
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• cone responses to bright-light stimuli are decreased at 16 weeks compared to controls
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• in retina pigmented epithelium (RPE) cells of mutants, degenerating phagosomes with undigested photoreceptor outer segment (POS) material are observed in contrast to controls where POS are in single-membrane phagosomes
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• in retina pigmented epithelium (RPE) cells of mutants, degenerating phagosomes with undigested photoreceptor outer segment (POS) material are observed in contrast to controls where POS are in single-membrane phagosomes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• exacerbation of renal inflammation in unilateral ureteric obstruction (UUO)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• goblet cells exhibit increased mucin accumulation compared with control cells
• however, the number of goblet cells is normal and hydrogen peroxide treatment normalizes mucin levels
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• goblet cells exhibit increased mucin accumulation compared with control cells
• however, the number of goblet cells is normal and hydrogen peroxide treatment normalizes mucin levels
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some mice die after 3 weeks
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• ubiquitin-positive inclusions are found in the thalamus pon, medulla, dorsal root ganglion, midbrain, cerebral cortex, hippocampus (especially in CA3 and CA4), striatum and olfactory bulb
autophagosomes formation in the brain is impaired
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• axonal swelling
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• axonal swelling in the posterior thalamic nucleus
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• axonal swelling
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• axonal swelling
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• loss of pyramidal cells in the cerebral cortex
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• apoptosis is detected in granular cells
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• axonal swelling in the cerebral cortex, nucleus gracilis, posterior thalamic nucleus, hippocampus, inferior colliculus, tricaudal pons and reticular nucleus
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• however, few degenerating Purkinje cells exhibit inclusions
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• ubiquitin-positive inclusions are found in the thalamus pon, medulla, dorsal root ganglion, midbrain, cerebral cortex, hippocampus (especially in CA3 and CA4), striatum and olfactory bulb
• inclusions are time-dependent and are more limited in newborns than in adults
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• progressive motor and behavioral deficits after three weeks of age
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• progressive motor deficits after three weeks of age including ataxia and a decrease in mean stride length
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• when suspended by their tails
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• coordination, balance and grip strength are impaired in a rotarod and wire hang task
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• grip strength is impaired in a rotarod and wire hang task
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• autophagosomes formation in the brain is impaired
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• body weight is about 1.5-times lower than that of wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• aberrant, disorganized granules as well as decreased granule numbers are observed in these mice
• virtually all Paneth cells have lysozyme localized throughout the cell instead of being discretely packaged within vesicles
• Paneth cells also have degenerating mitochondria, loss of granules and the frequent absence of apical microvilli
• adjacent crypt lumen often contains intact Paneth granules and cytoplasm, which is a phenomenon not observed in wild-type controls
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• autophagy by the ileal epithelium is severely reduced in these mice
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• autophagy by the ileal epithelium is severely reduced in these mice
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• aberrant, disorganized granules as well as decreased granule numbers are observed in these mice
• virtually all Paneth cells have lysozyme localized throughout the cell instead of being discretely packaged within vesicles
• Paneth cells also have degenerating mitochondria, loss of granules and the frequent absence of apical microvilli
• adjacent crypt lumen often contains intact Paneth granules and cytoplasm, which is a phenomenon not observed in wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cardiomyocyte fiber cross-sectional area is increased following tamoxifen treatment
• however, cardiomyocyte fibers are otherwise normal
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• increase in the heart to body weight ratio following tamoxifen treatment
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• following tamoxifen treatment
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• following tamoxifen treatment
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• calcium cycling is impaired following tamoxifen treatment
• decrease in the autophagy levels following tamoxifen treatment
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• increase in the lung to body weight ratio following tamoxifen treatment
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• cardiomyocyte fiber cross-sectional area is increased following tamoxifen treatment
• however, cardiomyocyte fibers are otherwise normal
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• following tamoxifen treatment
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• increase in the heart to body weight ratio following tamoxifen treatment
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• increase in the lung to body weight ratio following tamoxifen treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• cauda epididymal sperm number is reduced by ~60% relative to controls
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• cauda epididymal sperm show multiple abnormalities, including distorted and round heads, abnormal flagella, double heads, and sperm bundles
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• 20-30% of cauda epididymal sperm display abnormal flagella
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• some epididymal sperm show a short flagellum with a bulb at the tip of the tail
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• some cauda epididymal sperm exhibit a discontinuous accessory structure in the midpiece
• some sperm show a large vesicle at the midpiece
• cross-sections of two or more axonemes are seen in one cell, some of which are surrounded with disconnected mitochondria
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• mitochondria staining of cauda epididymal sperm revealed abnormal mitochondrial sheath formation: discontinuous and bundle forms of mitochondria signals are observed
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• 23.12% sperm exhibit unsheathed flagella at the principal piece
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• some epididymal sperm show a short flagellum with a bulb at the tip of the tail
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• ~50% of cauda epididymal sperm display misshapen heads, including round, swollen or bent heads
• in some sperm, significant mitochondrial staining is present at the head region, suggesting that the middle pieces and tails are coiling around the heads
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• cauda epididymal sperm exhibit abnormal acrosome formation: peanut-lectin (an acrosome marker) aggregates around the nucleus indicating abnormal acrosome localization
• TEM analysis revealed abnormally shaped acrosomes in developing spermatids
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• distorted and round heads are observed
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• cauda epididymal sperm exhibit an abnormally formed chromatin structure
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• some sperm exhibit double heads
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• some elongating spermatids fuse into giant cells
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• only few sperm are motile but exhibit markedly reduced motility
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• only a small % of epididymal sperm are motile versus >80% in controls
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• adult testis-to-body weight ratio is slightly lower than that of control males
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• testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity
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• spermatogenesis defects are first observed in step 10-14 elongating spermatids
• abnormal nuclear shapes start appearing with mixing of step 9 and 12 spermatids in stage XII
• large residual bodies are sloughed into the lumen and found even in stages XI-XI
• step 16 spermatids show retention in the epithelium in stages IX-XII
• some elongating spermatids fuse into giant cells; multiple elongating spermatids are wrapped in one cell membrane, indicating failure of individualization
• sloughing of cytoplasm or cytoplasm with attached immature elongating spermatids into the lumen is observed
• however, no major defects are observed in mitosis or meiosis
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• 33.29% of epididymal sperm aggregate into sperm bundles
• cauda epididymal sperm show loss of sperm individualization: two or more axonemes are frequently wrapped in one cell membrane
• in the seminiferous tubules, multiple elongating spermatids share a single cell membrane indicating failure of individualization
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• step 16 spermatids show retention in the epithelium rather than being released by spermiation in stages IX-XII
• impaired release of sperm into the seminiferous tubule lumen is likely due to failure to remove intercellular bridge components, as a result of disrupted autophagy activity
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• cauda epididymal lumen is filled with sloughed germ cells, large cytoplasmic bodies, and spermatozoa with disorganized heads and tails
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• 3 of six 2-mo-old males did not sire any offspring during 1 month of mating with wild-type females
• 9 of 11 older males did not sire any pups through 3 months of breeding
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• 3 of six 2-mo-old males sired only 5, 1, and 8 pups, respectively, totaling 14 pups during one month of mating with wild-type females
• one 3- to 5-month-old male sired 10 pups and one 5- to 7-month-old male sired one pup, respectively, through 3 months of breeding
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• cauda epididymal sperm number is reduced by ~60% relative to controls
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• cauda epididymal sperm show multiple abnormalities, including distorted and round heads, abnormal flagella, double heads, and sperm bundles
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• 20-30% of cauda epididymal sperm display abnormal flagella
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|
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• some epididymal sperm show a short flagellum with a bulb at the tip of the tail
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|
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• some cauda epididymal sperm exhibit a discontinuous accessory structure in the midpiece
• some sperm show a large vesicle at the midpiece
• cross-sections of two or more axonemes are seen in one cell, some of which are surrounded with disconnected mitochondria
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|
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• mitochondria staining of cauda epididymal sperm revealed abnormal mitochondrial sheath formation: discontinuous and bundle forms of mitochondria signals are observed
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• 23.12% sperm exhibit unsheathed flagella at the principal piece
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|
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• some epididymal sperm show a short flagellum with a bulb at the tip of the tail
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|
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• ~50% of cauda epididymal sperm display misshapen heads, including round, swollen or bent heads
• in some sperm, significant mitochondrial staining is present at the head region, suggesting that the middle pieces and tails are coiling around the heads
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|
|
• cauda epididymal sperm exhibit abnormal acrosome formation: peanut-lectin (an acrosome marker) aggregates around the nucleus indicating abnormal acrosome localization
• TEM analysis revealed abnormally shaped acrosomes in developing spermatids
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• distorted and round heads are observed
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|
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• cauda epididymal sperm exhibit an abnormally formed chromatin structure
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|
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• some sperm exhibit double heads
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• some elongating spermatids fuse into giant cells
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• testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity
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• only few sperm are motile but exhibit markedly reduced motility
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• only a small % of epididymal sperm are motile versus >80% in controls
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• testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity
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• adult testis-to-body weight ratio is slightly lower than that of control males
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• testicular expression of autophagosome marker LC3A/B-II is significantly decreased while expression of autophagy receptor SQSTM1/p62 is significantly increased, indicating a reduction in testicular autophagy activity
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/30/2024 MGI 6.23 |
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