Analysis Tools
growth/size/body
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• mice fail to gain weight after 1 week of age
• mice treated with a small molecule Eif2b activator, 2BAct, catch up to wild-type weights 2 weeks after beginning treatment
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behavior/neurological
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• in a beam-crossing test, mice show increased beam-crossing time and more foot slips and falls from the beam at 23 weeks, but not 8-19 weeks, and by 26 weeks, some mice completely fail to cross the beam within the trail time
• mice treated with 2BAct show normal performance on the beam-crossing test
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• mice begin to show a trend towards shorter hang times at 23 weeks of age and significant decrease in hang time at 26 weeks of age, indicating progressive strength deficits
• mice treated with 2BAct show normal performance on the inverted grid test
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nervous system
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• mice show increased reactive gliosis in the corpus callosum and spinal cord
• 2BAct treatment prevents reactive gliosis
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• marker analysis indicates that the integrated stress response is induced at 2.5, 5, and 7 months, but not at P14, in the cerebellum, forebrain, midbrain, and hindbrain; stress response precedes the appearance of pathology
• greater integrated stress response is seen in the spinal cord than in the cerebellum and the integrated stress response is activated in astrocytes and myelinating oligodendrocytes
• treatment with 2BAct abolishes integrated stress response in the cerebellum and spinal cord
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• reduction in myelin, with a 33% reduction in corpus callosum and 58% reduction in cervical/thoracic spinal cord
• 2BAct treatment maintains myelin levels at 91% and 85% of wild-type in the corpus callosum and spinal cord, respectively, indicating prevention of myelin loss
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| leukoencephalopathy with vanishing white matter | DOID:0060868 |
OMIM:PS603896 |
J:278928 | |
