behavior/neurological
• at 8-12 weeks of age, homozygotes display a significantly impaired performance on the accelerating Rotarod relative to wild-type mice, even after several trials
• administration of SKF38393 (a D1 dopaminergic agonist; 25 or 50 mg/kg), fails to improve Rotarod performance in both wild-type and mutant mice
• administration of cabergoline (0.2 or 1.0 mg/kg), a D2 dopaminergic agonist, selectively restores Rotarod performance of mutant mice to wild-type levels, but has no effect on wild-type mice
• no choleric or dystonic movements are observed in the tail suspension test
|
• at 8-12 weeks of age, homozygotes display a small but significant reduction in vertical open field locomotor activity relative to wild-type mice
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• at 8-12 weeks of age, homozygotes display a small but significant reduction in horizontal open field locomotor activity relative to wild-type mice
• administration of SKF38393 (25 or 50 mg/kg), a D1 dopaminergic agonist, elicits a significantly greater ("supersensitive") locomotor activity response in mutant mice relative to wild-type mice
• administration of cabergoline (0.2 or 1.0 mg/kg), a D2 dopaminergic agonist, has no effect on locomotor activity, although both wild-type and mutant mice display a tendency of small increases
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bradykinesia
(
J:83301
)
• at 8-12 weeks of age, homozygotes show significant bradykinesia in the pole test; when mice are placed head upward on the top of a rough surfaced pole, both Tturn (the time until mice turn completely downward) and TLA (the time until mice climb down to the floor), are prolonged by 3-fold relative to wild-type values
• both SKF38393 and cabergoline improve pole test performance in mutant mice; the latter induces a drastic improvement even with a lower dose (0.2 mg/kg)
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homeostasis/metabolism
• at 8-12 weeks of age, homozygotes display a marked loss of adenylyl cyclase activity in a striatum-specific manner with a small increase in the expression of other adenylyl cyclase isoforms
• D1 dopaminergic agonist-stimulated adenylyl cyclase activity is attenuated, along with a reduction in the expression of the D1 dopaminergic receptor and Gsalpha
• D2 dopaminergic agonist-mediated inhibition of adenylyl cyclase activity is blunted
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Parkinson's disease | DOID:14330 |
OMIM:PS168600 |
J:83301 |