Analysis Tools
mortality/aging
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• although present at normal Mendelian ratios at E18.5, most homozygotes die shortly after birth due to cardiorespiratory failure
(J:244440)
• only 4% of homozygotes are obtained from heterozygous matings at 2 weeks of age
(J:244440)
• pups show 90% mortality due to respiratory failure; the 10% of pups that survive thrive and reach a regular life span
(J:300001)
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muscle
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• at 15-20 weeks of age, male mice show a 7-fold increase of glycogen levels in cardiac muscle relative to wild-type controls
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• at 15-20 weeks of age, male mice show a 4-fold increase of glycogen levels in skeletal muscle relative to wild-type controls
• glycogen granules isolated from skeletal muscle are larger and extend over a wide range of sizes, with up to a 4-fold greater radius than that in wild-type controls
• EM revealed accumulation of large glycogen particles in the intermyofibrillar space of skeletal (quadriceps) muscle
• both soleus and EDL muscles show increased glycogen levels relative to wild-type muscles, with no significant difference in muscle weights
• however, no changes in the proportion of fiber types are observed in soleus and EDL muscles
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• slow-twitch soleus muscle generates a ~2-fold greater isometric force than its wild-type control at all stimulation frequencies tested, suggesting a switch of the oxidative soleus toward a more glycolytic type
• in contrast, fast-twitch EDL muscle generates a force similar to that of wild-type controls
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homeostasis/metabolism
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• in spite of increased skeletal muscle glycogen level, mice reach exhaustion earlier than wild-type controls in a treadmill endurance test
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• mice cover a shorter distance than wild-type controls in a treadmill endurance test
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• adult mice show decreased lipid oxidation esp. during the light phase
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• adult mice show decreased energy expenditure both during the light and dark phase
• however, body weight, fat:lean body mass, food intake and locomotor activity are normal
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• adult mice show lower carbon dioxide production both during the light and dark phase
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• adult mice show lower oxygen consumption both during the light and dark phase
• however, the respiratory exchange ratio (RER) is normal
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• adult mice show decreased glucose oxidation esp. during the dark phase
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• unexpectedly, mice are able to synthesize glycogen, as shown by normal glycogen levels in liver and brain relative to wild-type controls
• mass spectrometry-based analysis showed that glycogen is synthesized without a protein primer
• however, glycogen accumulation does not increase progressively with age in any tissue (liver, brain, skeletal or cardiac muscle)
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• at 15-20 weeks of age, male mice show a 7-fold increase of glycogen levels in cardiac muscle relative to wild-type controls
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• levels of glycogen are significantly decreased in lungs from early pseudoglandular stage onwards (E14.5) and are 60% lower than controls at E18.5
• lungs of surviving pups show a 20% reduction in glycogen content
• lungs of dead pups contain about 50% of glycogen of wild-type pups
• however, glycogen content is normal is surviving adults
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• at 15-20 weeks of age, male mice show a 4-fold increase of glycogen levels in skeletal muscle relative to wild-type controls
• glycogen granules isolated from skeletal muscle are larger and extend over a wide range of sizes, with up to a 4-fold greater radius than that in wild-type controls
• EM revealed accumulation of large glycogen particles in the intermyofibrillar space of skeletal (quadriceps) muscle
• both soleus and EDL muscles show increased glycogen levels relative to wild-type muscles, with no significant difference in muscle weights
• however, no changes in the proportion of fiber types are observed in soleus and EDL muscles
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• at the point of exhaustion following treadmill exercise, mice show a greater (~2-fold) reduction of glycogen content in skeletal muscle than wild-type controls, suggesting an overall glycolytic shift in muscle metabolism
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behavior/neurological
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• in spite of increased skeletal muscle glycogen level, mice reach exhaustion earlier than wild-type controls in a treadmill endurance test
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• mice cover a shorter distance than wild-type controls in a treadmill endurance test
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cellular
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• adult soleus muscle exhibits lower oxygen consumption affecting all mitochondrial states; these lower levels are comparable to those in wild-type fast-twitch EDL muscle
• AMP/ATP and ADP/ATP ratios are decreased in soleus muscle, approaching those found in wild-type EDL muscle
• soleus muscle shows no reduction in mitochondrial number or OXPHOS proteins
• EDL muscle shows normal oxygen consumption values with no change in AMP/ATP and ADP/ATP ratios
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• adult mice show decreased lipid oxidation esp. during the light phase
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cardiovascular system
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• at 15-20 weeks of age, male mice show a 7-fold increase of glycogen levels in cardiac muscle relative to wild-type controls
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• most homozygotes die shortly after birth due to cardiorespiratory failure
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respiratory system
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• lungs show reduced presence of SP-B and SP-C surfactant proteins
• non-surviving pups show altered surfactant proteins SP-B and SP-C distribution
• however, lung morphology is preserved at E14.5 and at the saccular stage (E18.5), and no differences in cell morphology or apoptosis are seen in lungs at E18.5 and lung morphology and SP-B and SP-C levels are normal is surviving adults
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• levels of glycogen are significantly decreased in lungs from early pseudoglandular stage onwards (E14.5) and are 60% lower than controls at E18.5
• lungs of surviving pups show a 20% reduction in glycogen content
• lungs of dead pups contain about 50% of glycogen of wild-type pups
• however, glycogen content is normal is surviving adults
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• accumulation of multivascular bodies (pre-lamellar body organelles), composite bodies (an intermediate organelle containing both vesicles and lamellae) and mitochondria in the cytoplasm of type II pneumocytes
• however, type II pneumocytes of the lungs contain lamellar bodies with similar structure to those in controls
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• lamellar bodies in type II pneumocytes are smaller
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atelectasis
(
J:300001
)
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• sacculi of dead pups are collapsed
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• surviving pups exhibit open sacculi but have thicker septa and lungs are not expanded to the same extent as in wild-type mice
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• most pups show difficulty in breathing upon birth, characterized by rapid and shallow breaths
• most lungs from pups that die sink in water indicating no air-inflation
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• most homozygotes die shortly after birth due to cardiorespiratory failure
(J:244440)
• pups die due to respiratory failure
(J:300001)
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| glycogen storage disease XV | DOID:0050579 |
OMIM:613507 |
J:300001 | |
