Analysis Tools
homeostasis/metabolism
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• on a low-folate diet, heterozygotes exhibit siginifcantly elevated plasma total homocysteine levels relative to wild-type mice
(J:64885)
• however, on a control diet, heterozygotes display normal plasma total homocysteine levels relative to wild-type mice
(J:64885)
• serum total homocysteine levels are slightly increased compared to in wild-type mice
(J:166184)
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cardiovascular system
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• capillary tufts and dilations are seen in peripheral areas of the retina
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• at 24 weeks of age, mice have large vessels that manifest numerous small constrictions along their length, giving them a saccular, beaded appearance instead of smooth edges as in wild-type mice
• increase in blood vessel tortuosity in the retina
• increase in venule, but not arteriole, width, in the retina and a decrease in the ratio of arteriole/venule width
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• a well-defined branching pattern from the central retinal artery is not seen in mutant mice and a large capillary-free zone is seen in the central part of the retina
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• by 1 year of age, many microaneurysms are seen in the capillary bed and there is evidence of new blood vessels
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• at 52 weeks of age, mice show evidence of new vessels in the retina and marker analysis indicates neovascularization in multiple layers of the retina, including the ganglion cell and inner nuclear layers
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• in the retina, pericytes are partially detached and extend processes away from the endothelial cells
• retinal blood vessels show pericytes with degenerated cytoplasmic remnants and occasionally ghosts of former pericytes
• retinas show pericyte disruption in nearly all blood vessels (>90%) compared to <5% in wild-type mice
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• increase in venule, but not arteriole, width, in the retina and a decrease in the ratio of arteriole/venule width
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• evidence of vascular occlusion in the retina, ischemic nodules, and hemorrhagic spots
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• on a low-folate diet (~50% reduction in plasma folate levels), heterozygotes display a significant endothelial vasomotor dysfunction associated with moderate hyperhomocysteinemia
• endothelial vasomotor dysfunction is noted only in mice with a combined defect in homocysteine remethylation (produced by dietary folate deficiency) and homocysteine transsulfuration (produced by heterozygous deficiency)
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• vascular leakage is seen within the capillary bed of the retina at 24 weeks of age
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• on a control diet, heterozygotes show normal relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine relative to wild-type mice
• however, on a low-folate diet, heterozygotes exhibit impaired maximal relaxation of aortic rings in response to acetylcholine relative to wild-type mice (58 9% vs 84 4%, respectively)
• no significant differences in relaxation to nitroprusside or contraction to the thromboxane A2 analog U-46619 are observed between wild-type and heterozygous mice fed either control or low-folate diets
• no significant differences in aortic thrombomodulin activity are observed between wild-type and heterozygous mice fed either control or low-folate diets
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muscle
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• on a control diet, heterozygotes show normal relaxation of aortic rings in response to the endothelium-dependent vasodilator acetylcholine relative to wild-type mice
• however, on a low-folate diet, heterozygotes exhibit impaired maximal relaxation of aortic rings in response to acetylcholine relative to wild-type mice (58 9% vs 84 4%, respectively)
• no significant differences in relaxation to nitroprusside or contraction to the thromboxane A2 analog U-46619 are observed between wild-type and heterozygous mice fed either control or low-folate diets
• no significant differences in aortic thrombomodulin activity are observed between wild-type and heterozygous mice fed either control or low-folate diets
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nervous system
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• Muller cell activation in the retina
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• astrocytes in the retina have diffuse branching patterns and a ragged appearance
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• retinas show an increase in astrocytes which have diffuse branching patterns and a ragged appearance
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• fluorescein angiography of retinas shows leakage of fluorescein at 24 weeks of age that progresses with age indicating vascular leakage
• marker analysis indicates disruption of the inner blood-retinal barrier
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vision/eye
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• fluorescein angiography of retinas shows leakage of fluorescein at 24 weeks of age that progresses with age indicating vascular leakage
• marker analysis indicates disruption of the inner blood-retinal barrier
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• disruption of retinal architecture and the inner retina has an uneven appearance in 52 week old mice
• retinas show hypoxic areas, particularly in the regions where there is abnormal vasculature
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• capillary tufts and dilations are seen in peripheral areas of the retina
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• at 24 weeks of age, mice have large vessels that manifest numerous small constrictions along their length, giving them a saccular, beaded appearance instead of smooth edges as in wild-type mice
• increase in blood vessel tortuosity in the retina
• increase in venule, but not arteriole, width, in the retina and a decrease in the ratio of arteriole/venule width
|
|
• a well-defined branching pattern from the central retinal artery is not seen in mutant mice and a large capillary-free zone is seen in the central part of the retina
|
|
• by 1 year of age, many microaneurysms are seen in the capillary bed and there is evidence of new blood vessels
|
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• at 52 weeks of age, mice show evidence of new vessels in the retina and marker analysis indicates neovascularization in multiple layers of the retina, including the ganglion cell and inner nuclear layers
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• Muller cell activation in the retina
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• reactive gliosis in the retina
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• disruption of retinal architecture is seen in 52 week old mice, with unusual structures within the vitreous and debris in the vitreous cavity
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• ischemia in the central retina and new blood vessel formation in the periphery
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| homocystinuria | DOID:9263 |
OMIM:236200 OMIM:236250 |
J:213631 | |
