Analysis Tools
mortality/aging
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• die between 2 and 5 weeks of age
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behavior/neurological
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• ataxia ranging in severity from mice being unable to right themselves to those with splayed rear legs
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• mice occasionally exhibit seizure episodes in which they run wildly before collapsing
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cardiovascular system
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• arteries, veins, and intervening vessels of the middle-cerebral vessels are enlarged
• vessel enlargement occurs before hemorrhage, neuronal cell death, or signs of neurological dysfunction
• vessel enlargement correlates with hemorrhage, with them most large vessels in the cerebellum, followed by neocortex
• vessel density is decreased significantly in the cerebellum, and progressively less so in the neocortex and brainstem
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• enlarged and tangled vessels resembling brain arteriovenous malformations
• arteriovenous shunts in the brain
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hemorrhage
(
J:139943
)
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• hemorrhage in the brain of all mutants, most often in the cerebellum, followed by the neocortex, but never in the brainstem
• hemorrhage is more widespread than neurological dysfunction, seen in all ill mutants without ataxia and is most severe in mice ill before P22
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• blood is seen in the ventricle of 4 of 11 ill mice before P21
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• increase in carotid blood velocity in all mutants by 3 weeks of age
• carotid blood velocity increases between P17 and P21 and at P21, velocity in mutants with neurological dysfunction is higher than mutants without the dysfunction
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homeostasis/metabolism
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• thrombosis is seen in hemorrhagic areas
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nervous system
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• arteries, veins, and intervening vessels of the middle-cerebral vessels are enlarged
• vessel enlargement occurs before hemorrhage, neuronal cell death, or signs of neurological dysfunction
• vessel enlargement correlates with hemorrhage, with them most large vessels in the cerebellum, followed by neocortex
• vessel density is decreased significantly in the cerebellum, and progressively less so in the neocortex and brainstem
|
|
• foci of pyknotic and karyorectic nuclei in the midbrain
• macrophage infiltrations in the midbrain
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• foci of pyknotic and karyorectic nuclei in the neocortex
• macrophage infiltrations in the neocortex
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• foci of pyknotic and karyorectic nuclei in the Purkinje and granular layers of the cerebellum
• macrophage infiltrations in the Purkinje and granular layers of the cerebellum
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• signs of calcification in the brain
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• neurological dysfunction is seen in 27 of 107 mutants, including ataxia and seizures
• all but one of the cases of ataxia and seizure occur before P22
• sick mutants at P20-21 treated with doxycycline to repress Notch4 expression appear healthy and active at P35 and P64
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• mice occasionally exhibit seizure episodes in which they run wildly before collapsing
|
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• blood is seen in the ventricle of 4 of 11 ill mice before P21
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• neuronal cell death adjacent to hemorrhage
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cellular
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• neuronal cell death adjacent to hemorrhage
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| arteriovenous malformations of the brain | DOID:0060688 |
OMIM:108010 |
J:139943 | |
