Analysis Tools
behavior/neurological
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• mice treated with a high dose of AP20187 daily starting at P10 exhibit severe tremoring starting around P14
• mice treated with AP20187 at P10 and then treatment stopped at P15 show loss of tremoring staring around P24 and survive
• however, mice treated with AP20187 daily starting on P28 do not show obvious tremors
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cellular
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• protein biosynthesis in the optic nerve from 18 day old mice treated with a high dose of AP20187 is suppressed, while a lose dose of AP20187 slightly, but significantly, decreases protein biosynthesis
• however, protein biosynthesis in the sciatic nerve is not altered in AP20187 treated mice
• protein biosynthesis in the optic nerve is suppressed in mice treated daily with AP20187 at 8 weeks for up to 3 weeks
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homeostasis/metabolism
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• protein biosynthesis in the optic nerve from 18 day old mice treated with a high dose of AP20187 is suppressed, while a lose dose of AP20187 slightly, but significantly, decreases protein biosynthesis
• however, protein biosynthesis in the sciatic nerve is not altered in AP20187 treated mice
• protein biosynthesis in the optic nerve is suppressed in mice treated daily with AP20187 at 8 weeks for up to 3 weeks
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mortality/aging
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• mice treated with a high dose of AP20187 daily starting at P10 die by P24
• however, mice treated with AP20187 daily starting on P28 survive for at least 2 weeks
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• mice treated with AP20187 daily starting on P7 die within 5 days of start of treatment
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nervous system
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• size of the CNS white matter is slightly reduced in mice treated daily with AP20187 at 8 weeks for up to 3 weeks
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• about 35% of oligodendrocytes in the CNS white matter of AP20187 treated mice exhibit a foamy morphology, with cells having abundant cytoplasm filled with circular, membranous structures and an oval nucleus with condensed chromatin
• a few foamy oligodendrocytes show characteristics of apoptosis, including highly condensed chromatin mass, nuclear fragmentation, and shrunken cytoplasm
• number of oligodendrocytes is moderately, but not significantly, reduced in the CNS white matter
• however, mice treated daily with AP20187 at 8 weeks for up to 3 weeks do no exhibit foamy oligodendrocytes in the CNS white matter
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• diameter of axons in the CNS white matter is decreased in mice treated daily with AP20187 at 8 weeks for up to 3 weeks, however no effect on thickness of myelin sheaths is seen
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• thickness of myelin sheaths is decreased in mice treated with AP20187 starting at P10
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• degree of myelination in the CNS white matter, including the spinal cord, cerebellum, and corpus callosum, is decreased in AP20187 treated mice, indicating hypomyelination
• reduction in the percentage of myelinated axons in the white matter in 20 day old mice that began daily AP20187 treatment starting at P10
• G-ratio of myelinated axons in the CNS white matter is increased in mice treated with AP20187 starting at P10
• however, the myelination process in the peripheral nervous system is not affected in mice treated with AP20187
• treatment with AP20187 at 8 weeks of age for up to 3 weeks results in a slight reduction in the percentage of myelinated axons in the CNS white matter
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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:216298 | |
