Phenotypes Associated with This Genotype

Genotype
MGI:2662300

• Allelic Composition: Adcy5^tm1Yish/Adcy5^tm1Yish
• Genetic Background: involves: 129X1/SvJ * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

impaired coordination ( J:83301 )

• 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

decreased vertical activity ( J:83301 )

• at 8-12 weeks of age, homozygotes display a small but significant reduction in vertical open field locomotor activity relative to wild-type mice

decreased locomotor activity ( J:83301 )

• 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

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 T_turn (the time until mice turn completely downward) and T_LA (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)

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:83301 )

• 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 G_salpha

• D2 dopaminergic agonist-mediated inhibition of adenylyl cyclase activity is blunted

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease		DOID:14330	OMIM:PS168600	J:83301