Analysis Tools
mortality/aging
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• infusion of bosentan an endothelin A/B receptor antagonist, into mutants undergoing nephrectomy prevents lethality observed in mutant controls after surgery
• surgical removal of 75% of renal mass by nephrectomy induces mortality in 100% of mutants, but wild-type animals display no lethality
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behavior/neurological
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• in the water maze tests, on day 1 of training, mutants have the lowest percentage of correctly finding the hidden platform and the longest latencies to find it; on the second day of training, mutants perform better than wild-type indicative of impairment in strategies rather than working memory
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• in black-white box tests, mutants spend significantly less time in the white section and time spent crossing between white and black sides is decreased
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• animals have severe equilibrium deficits evidenced by inablility to remain on rotating rod
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• in rotating rod tests, mutants fall off rod rapidly, while wild-type mice stay on rod for duration of observation
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• in open-field tests mutants show significantly increased locomotion; percentage of locomotion performed in the center of the arena is decreased
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hyperactivity
(
J:79046
)
nervous system
| N |
• cultured neural stem cells exhibit normal apoptosis
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• in cerebellar white matter, a discrete rarefaction of astrocyte processes is observed
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• in 10 day-old mutants the ultrastructure of Bergmann glia in the cerebellum is disturbed with poorly differentiated cell bodies; apical processes appear stunted and vascular end-feet are poorly developed
• in the cerebellum of adult mutants, most but not all Bergmann glia appear hypertrophic with thickened processes and lack of normal delicate appendages; Bergmann cells form large electron-lucent lakes with dendritic thorns and parallel fiber boutons embedded
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• around cell bodies of Purkinje cells, synapses of basket neurons are reduced in number and surface of cell bodies of neurons is occupied by dystrophic Bergmann glia
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• there are occasional necrotic cells with cell displaying early signs of degeneration
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• dendritic tree of many cells appears stunted with few dendritic thorns or smooth branchlets; with elecron microscopy, Purkinje cells display retracted spiny branchlets with a paucity of dendritic thorns and corresponding loss of parallel fiber synapses
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• in mutants some Purkinje cells are lacking; density appears reduced, but this is highly variable from one lobule to another
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• cultured E18.5 neurons have glial fibrillary acidic protein-immunoreactive filaments in astrocytes are sparse, irregularly arrayed, and sometimes disrupted
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embryo
| N |
• homozygotes develop normally showing normal histological sections of various organs such as lens, spleen, skeletal and cardiac muscle, lung, kidney, testis, skin, liver, intestine, blood and bone marrow and show normal hair growth and vibrissae development, wound healing, lens differentiation and adipogenesis
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reproductive system
| N |
• exhibit normal reproduction
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cardiovascular system
| N |
• heart weight is unaffected in mutants by surgery
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• 24 hours after nephrectomy, MAP is slightly but significantly decreased in mutants but not in wild-type controls
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• renal arteries (renal rings) show reduced maximal contraction in response to pharmacological concentrations of contractile agents endothelin-1 or phorbol dibutyrate; renal arterial rings show increased sensitivity (lower EC50 values) to contractile agents compared to controls
• pressure-induced arterial tone (constriction) is increased in surgically-treated mutants relative to controls
• mutant aortas show similar responses to controls
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• sensitivity of renal arteries in response to acetylcholine, a relaxing agent, is lower (higher IC50 values)
• flow-induced dilation in renal resistance arteries is reduced in surgically-treated mutants relative to controls
• mutant aortas show similar responses as controls
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cellular
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• fibroblasts 12.5- and 13.5-day old embryos are flatter than wild-type cells which have a spindle-shaped morphology
• mechanical stability of cells in response to distending forces is reduced compared to wild-type cells; mutant fibroblasts exhibit tearing of cytoplasm and rupture of plasma membrane in response to a distending force
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• fibroblasts display reduced contraction of collagenous lattices in collagen gel cultures compared to control cells; contraction forces developed by mutant cells are lower than those observed in wild-type cultures
• actin network formation and focal contact formation are impaired in mutant cells
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• cultured cells show 30% reduction in inherent motility in in vitro wound healing assays, and 40-60% reduction in chemotactic migration induced by PDGF or fibronectin compared to wild-type
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homeostasis/metabolism
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• 24 hours after surgical removal of 75% of renal mass by nephrectomy, plasma creatinine levels are higher than in treated controls
• infusion of bosentan an endothelin A/B receptor antagonist, into mutants undergoing nephrectomy results in plasma creatinine levels that are lower than untreated mice
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respiratory system
| N |
• lung wet and dry weights are not altered in mutants following surgery
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muscle
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• renal arteries (renal rings) show reduced maximal contraction in response to pharmacological concentrations of contractile agents endothelin-1 or phorbol dibutyrate; renal arterial rings show increased sensitivity (lower EC50 values) to contractile agents compared to controls
• pressure-induced arterial tone (constriction) is increased in surgically-treated mutants relative to controls
• mutant aortas show similar responses to controls
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• sensitivity of renal arteries in response to acetylcholine, a relaxing agent, is lower (higher IC50 values)
• flow-induced dilation in renal resistance arteries is reduced in surgically-treated mutants relative to controls
• mutant aortas show similar responses as controls
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