Analysis Tools
hematopoietic system
| N |
• hematological and plasma chemical analysis demonstrated no major abnormalities
• flow cytometry revealed no changes in the relative numbers of erythroid precursors, granulocytes, macrophages, or B cells in bone marrow of homozygous mutant mice
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homeostasis/metabolism
| N |
• homozygous mutant mice displayed a normal lipid metabolism; no changes in plasma levels of cholesterol and phospholipids were observed
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• unconjugated bilirubin levels were increased in homozygous null mice relative to wild-type; however, unconjugated bilirubin levels reverted to normal when mutant mice were fed a semisynthetic diet consisting of purified nutrients
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• homozygous mutant mice exhibited a novel type of protoporphyria
• in mutant mice, erythrocyte levels of the heme precursor and phototoxin protoporphyrin IX, which is structurally related to pheophorbide a, were elevated 10-fold
• transplantation with wild-type bone marrow cured the protoporphyria and alleviated the phototoxin sensitivity
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phototoxicity
(
J:80519
)
|
• when exposed to standard fluorescent light, all homozygous mutant mice developed phototoxic ear lesions 1 week after being fed with a "phototoxic" diet containing higher (10% or 20%) versus normal (5%) levels of alfalfa; occasionally, lesions appeared o n the tail, snout, and around the eyes
• all homozygous mutant mice were extremely (at least 100-fold) more sensitive to pheophorbide a (a phototoxic porphyrin catabolite of chlorophyll); the lowest dose at which phototoxicity occurred was 2 mg/kg/day
• at 16 mg/kg/day, ear lesions developed after 2 days, and after 3 days mutant mice developed edema of the head and became moribund; in contrast, phototoxicity was never observed in wild-type mice up to 200 mg/kg/day
• plasma levels of pheophorbide a were significantly increased in homozygous mutant mice fed with phototoxic or 20% alfalfa food compared with a "normal" food; in wild-type mice, plasma levels of pheophorbide a were not detectable on any of these diets
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liver/biliary system
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• unexpectedly, in homozygous mutants, the bile was red instead of yellow
• HPLC analysis demonstrated the red bile color was not caused by bilirubin or its conjugates
• the presence of red-colored bile was diet-dependent, because it disappeared in mice that were given a semisynthetic diet consisting of purified nutrients; interestingly, the red bile color reappeared following oral administration of (dark-green) pheophorbide a, suggesting that the red compound excreted in bile was a red chlorophyll catabolite or a related pheophorbide a metabolite
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integument
phototoxicity
(
J:80519
)
|
• when exposed to standard fluorescent light, all homozygous mutant mice developed phototoxic ear lesions 1 week after being fed with a "phototoxic" diet containing higher (10% or 20%) versus normal (5%) levels of alfalfa; occasionally, lesions appeared o n the tail, snout, and around the eyes
• all homozygous mutant mice were extremely (at least 100-fold) more sensitive to pheophorbide a (a phototoxic porphyrin catabolite of chlorophyll); the lowest dose at which phototoxicity occurred was 2 mg/kg/day
• at 16 mg/kg/day, ear lesions developed after 2 days, and after 3 days mutant mice developed edema of the head and became moribund; in contrast, phototoxicity was never observed in wild-type mice up to 200 mg/kg/day
• plasma levels of pheophorbide a were significantly increased in homozygous mutant mice fed with phototoxic or 20% alfalfa food compared with a "normal" food; in wild-type mice, plasma levels of pheophorbide a were not detectable on any of these diets
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| erythropoietic protoporphyria | DOID:13270 |
OMIM:177000 OMIM:300752 |
J:80519 | |
