Analysis Tools
pigmentation
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• agouti mice are khaki colored; nonagouti mice resemble homozygous pallid mice
• homozygotes display severe coat-color dilution
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• mutant melanosomes are reduced in number, smaller and less melanized than wild-type
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• mutant melanosomes are reduced in number, smaller and less melanized than wild-type
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• mutant melanosomes appear immature and are severely reduced in number in the eye and skin, resulting in severe oculocutaneous albinism
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• homozygotes display abnormal melanosome formation both quantitatively and qualitatively
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• homozygotes display a severe reduction in skin and eye pigment relative to wild-type controls
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• mutant melanosomes are severely reduced in number throughout the retinal pigmented epithelium and choroid layers
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hematopoietic system
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• platelet ATP release is undetectable
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• loss of dense body electron density suggests a low platelet Ca2+ content
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• adult homozygotes show a 6-fold decrease in the number of dense bodies (delta granules) per platelet relative to wild-type controls
• most mutant platelets contain no visible dense bodies, although a small number have one or two
• in contrast, the number and size of alpha-granules remains normal
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• mutant platelet serotonin levels are reduced to ~3% of wild-type levels
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• platelet aggregation determined in whole blood by the impedance method in response to collagen (1 or 4 ug/mL) is reduced
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• mutant platelets show a marked deficiency of dense body contents
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homeostasis/metabolism
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• platelet ATP release is undetectable
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• loss of dense body electron density suggests a low platelet Ca2+ content
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• mutant platelet serotonin levels are reduced to ~3% of wild-type levels
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• platelet aggregation determined in whole blood by the impedance method in response to collagen (1 or 4 ug/mL) is reduced
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• mutant platelets show a marked deficiency of dense body contents
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• adult homozygotes exhibit significantly increased bleeding times relative to wild-type controls (15.9 +/- 2.9 min versus 1.5 +/- 0.6 min, respectively)
• however, all hematologic parameters, including WBC and RBC counts, hemoglobin, hematocrit, platelet counts and mean platelet volume, are normal
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vision/eye
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• mutant melanosomes are reduced in number, smaller and less melanized than wild-type
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• mutant melanosomes are severely reduced in number throughout the retinal pigmented epithelium and choroid layers
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• homozygotes display a marked reduction in the choroid layer relative to wild-type controls
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• mutant melanosomes are reduced in number, smaller and less melanized than wild-type
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behavior/neurological
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• ~75% of homozygotes exhibit abnormal postural and balance reflexes with variable severity, suggesting otolith defects
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• some homozygotes display balance deficits only upon handling and close observation
• others are unable to stand upright
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• some homozygotes display abnormal head tilting only upon handling and close observation
• others exhibit extreme leaning to one side
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renal/urinary system
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• in mutant kidneys, activity levels of beta-galactosidase, beta-glucuronidase and alpha-galactosidase are increased by 2.0- to 2.5-fold relative to wild-type controls
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liver/biliary system
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• in mutant livers, activity levels of alpha-galactosidase are increased by >2-fold relative to wild-type controls
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cellular
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• platelet ATP release is undetectable
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• homozygotes display a lysosomal secretion defect resulting in enzyme accumulation in the kidney and liver, but not spleen or platelets
• however, lysosomal protein trafficking studies indicate that the cellular distribution of AP-3 proteins and internalization of lysosomal-associated membrane protein 1(LAMP1) is normal in mutant fibroblasts
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• failure of mutant CNO protein to coassemble with pallidin in cultured fibroblasts from homozygous mutant mice indicates that BLOC-1 (biogenesis of lysosome-related organelles complex-1) is disrupted
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respiratory system
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• no gross pathologic abnormalities are detected in lung at 10 months of age
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integument
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• agouti mice are khaki colored; nonagouti mice resemble homozygous pallid mice
• homozygotes display severe coat-color dilution
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Hermansky-Pudlak syndrome | DOID:3753 |
OMIM:PS203300 |
J:61187 | |
