Analysis Tools
mortality/aging
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• stated to have a phenotype identical to Dbhtm1Rpa however no data is provided in J:30404
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growth/size/body
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Allele Symbol Allele Name Allele ID |
Dbhtm2(Th)Rpa targeted mutation 2, Richard D Palmiter MGI:1928960 |
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| Summary |
6 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• stated to have a phenotype identical to Dbhtm1Rpa however no data is provided in J:30404
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• bilateral injection of CAVCre (cre recombinase delivered by a canine adenovirus vector, efficient uptake into dopaminergic neurons) into the central region of the caudate putamen allows mice to survive without L-DOPA treatment
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• after viral Cre treatment and a 24 hour fast, mice consume less food when a standard chow diet is provided but a similar amount, compared to wild-type controls, when a higher-fat breeder chow diet is provided
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• for the first 4 days after viral Cre treatment mice consume more than wild-type controls
• after viral Cre treatment on a highly palatable liquid diet mice consume large meals and tend to lick faster than wild-type controls
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• seen in an open field test after viral Cre treatment
• however, other measures of anxiety (time spent in open arms of a maze and entry into open arms) are similar to controls
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• after viral Cre treatment performance on a rotarod improves with practice but is consistently worse than in wild-type controls
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• hyperactive after viral Cre treatment
• L-DOPA treatment increased activity in both Cre treated and untreated mice but not in wild-type controls
• however, exploratory locomotor response is similar to controls
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• prior to viral cre treatment and for 1 - 3 months after viral cre treatment mice weigh less than controls
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• after viral cre treatment, mice gain weight more rapidly than controls reaching body weights similar to controls by 1 - 3 months after treatment
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• after viral cre treatment dopamine levels in the brain to about 55% of controls and dopamine metabolite levels are also partially restores
• evoked dopamine release in the sections from the caudate putamen is about 30% of controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• conditioned place aversion to the KOR agonist U50,488 is slightly but significantly increased compared to littermate controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• without viral cre injection, phenotype is stated to be indistinguishable from mice homozygous for Thtm1Rpa and heterozygous for Dbhtm2(Th)Rpa
• mice die within 3 days of stopping L-DOPA treatment
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• severely hypoactive
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• cessation of L-DOPA treatment results in weight loss
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• dopamine levels are 0.56% of controls
• dopamine metabolite levels are also reduced
• evoked dopamine release in caudate putamen sections is absent
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all die by 4 weeks of age
• twice daily treatment with 50 mg/kg L-dihydroxyphenylalanine (L-DOPA) starting around P15 rescues the lethality
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• at P10 - P15
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• at P16, body weight is 70% of control littermates
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• after P17 a negative growth rate is seen
• twice daily treatment with 50 mg/kg L-DOPA starting around P15 restores a nearly normal growth rate
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• injection with L-DOPA restores eating behavior with maximal intake during the first 2 hours after injection and cessation of eating by about 6 hours post injection
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• at P10 - P15
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• at P10 - P15
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• at P10 - P15, travel only about 3m/hr compared to 23 m/hr in controls
• however at P16, reflexion, corneal, startle, righting, grasping, and placing reflexes are all similar to controls, balance is not impaired, and no tremors are seen
• within 15 minutes of injection of L-DOPA activity levels increase peaking at about 1 hour post injection and then decreasing so that by 12 hours post injection mice are hypoactive
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• make about 280 stereotypical beam breaks per hour compared to about 700 per hour for controls
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• brain size is reduced and neurons are slightly more compact; however, dopaminergic neuron and striatum morphology are similar to controls
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• expression levels of tachykinin 1 and dynorphin are decreased in the striatum
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• dopamine levels in the brain are low; however, levels of norepinephrine in the brain, heart, salivary glands, and adrenal glands are similar to controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 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)
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• 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
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• 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
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• 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
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• 1 hour after L-DOPA treatment a decrease in response in the paw pinch assay is seen
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• 24 or more hours after L-DOPA treatment rotarod and pole test performance are poor
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• 24 hours after L-DOPA treatment 1- and 4-limb akinesia is increased compared to controls
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• 24 or more hours after L-DOPA treatment the gait is awkward
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• 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
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• 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
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• 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
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• 24 hours after L-DOPA treatment forelimb catalepsy is increased compared to controls
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 08/21/2024 MGI 6.24 |
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