Phenotypes Associated with This Genotype

Genotype
MGI:3654636

• Allelic Composition: Dbh^tm2(Th)Rpa/Dbh⁺; Th^tm1Rpa/Th^tm1Rpa
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

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

mortality/aging

premature death ( J:58125 )

• can be maintained for at least 1.5 years with daily treatment of 50 mg/kg L-DOPA and feeding with breeder chow (4.35 kcal/g)

behavior/neurological

impaired behavioral response to addictive substance ( J:58125 )

• 19 hours after L-DOPA treatment a single dose of amphetamine (5mg/kg) induces a shorter increase in activity (1 hour compared to 2 hours in controls) and a second dose of amphetamine fails to alter activity unlike in controls

decreased food intake ( J:58125 )

• during the first 24 hours after L-DOPA treatment food intake is similar to controls but during the next 24 hours intake decreases to about 10% of wild-type

• food intake is proportional to L-DOPA dose up to 100 mg/kg

decreased compensatory feeding amount ( J:58125 )

• if food is with held for 3 or 6 hours after L-DOPA treatment mice compensate by consuming more food in the next 3 hours to consume about the same amount of food as when food is continually available; however no compensation if food is with held for 9 hours

• after a 30 hour fast when presented with a high sucrose, high-fat diet mice begin to consume food but cease eating sooner and consume only about 25% of the amount eaten by wild-type mice

hyporesponsive to tactile stimuli ( J:58125 )

• 1 hour after L-DOPA treatment a decrease in response in the paw pinch assay is seen

impaired coordination ( J:58125 )

• 24 or more hours after L-DOPA treatment rotarod and pole test performance are poor

hunched posture ( J:58125 )

akinesia ( J:58125 )

• 24 hours after L-DOPA treatment 1- and 4-limb akinesia is increased compared to controls

abnormal gait ( J:58125 )

• 24 or more hours after L-DOPA treatment the gait is awkward

decreased locomotor activity ( J:58125 )

• in untreated mice or by 24 hours after L-DOPA treatment

• a second small peak of activity occurs between 24 and 40 hours after treatment however overall activity is decreased compared to controls

hyperactivity ( J:58125 )

• for 6 - 9 hours after L-DOPA treatment activity level is higher than in wild-type

• treatment with L-DOPA and carbidopa induces a biphasic increase in activity that is more prolonged than when L-DOPA is given alone; however, in wild-type mice L-DOPA and carbidopa treatment induces inactivity

increased stereotypic behavior ( J:58125 )

• treatment with L-DOPA and carbidopa induces intense stereotypic behavior (licking and chewing of paws) between 1 and 5 hours after treatment, no such behavior is seen in controls

catalepsy ( J:58125 )

• 24 hours after L-DOPA treatment forelimb catalepsy is increased compared to controls