Phenotypes associated with this allele

• Allele Symbol: Dbh^tm2(Th)Rpa
• Allele Name: targeted mutation 2, Richard D Palmiter
• Allele ID: MGI:1928960
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dbh^tm2(Th)Rpa/Dbh^tm2(Th)Rpa	Not Specified	MGI:3654635
cn2	Dbh^tm2(Th)Rpa/Dbh^+ Th^tm5Rpa/Th^tm5Rpa	involves: 129S4/SvJaeSor * C57BL/6	MGI:3654637
cx3	Dbh^tm2(Th)Rpa/Dbh^+ Th^tm5Rpa/Th^tm5Rpa	involves: 129S4/SvJaeSor	MGI:4414756
cx4	Dbh^tm2(Th)Rpa/Dbh^+ Th^tm5Rpa/Th^tm5Rpa	involves: 129S4/SvJaeSor * C57BL/6	MGI:3654638
cx5	Dbh^tm2(Th)Rpa/Dbh^+ Th^tm1Rpa/Th^tm1Rpa	involves: 129S7/SvEvBrd	MGI:2175827
cx6	Dbh^tm2(Th)Rpa/Dbh^+ Th^tm1Rpa/Th^tm1Rpa	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3654636

Genotype
MGI:3654635

hm1

• Allelic Composition: Dbh^tm2(Th)Rpa/Dbh^tm2(Th)Rpa
• Genetic Background: Not Specified

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

mortality/aging

postnatal lethality ( J:30404 )

embryonic lethality during organogenesis, incomplete penetrance ( J:30404 )

• stated to have a phenotype identical to Dbh^tm1Rpa however no data is provided in J:30404

growth/size/body

postnatal growth retardation ( J:30404 )

Genotype
MGI:3654637

cn2

• Allelic Composition: Dbh^tm2(Th)Rpa/Dbh⁺; Th^tm5Rpa/Th^tm5Rpa
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

mortality/aging

mortality/aging ( J:110806 )

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

behavior/neurological

abnormal eating behavior ( J:110806 )

decreased compensatory feeding amount ( J:110806 )

• 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

increased food intake ( J:110806 )

• 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

increased thigmotaxis ( J:110806 )

• 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

abnormal motor capabilities/coordination/movement ( J:110806 )

impaired coordination ( J:110806 )

• after viral Cre treatment performance on a rotarod improves with practice but is consistently worse than in wild-type controls

hyperactivity ( J:110806 )

• 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

growth/size/body

decreased body weight ( J:110806 )

• prior to viral cre treatment and for 1 - 3 months after viral cre treatment mice weigh less than controls

abnormal postnatal growth ( J:110806 )

• after viral cre treatment, mice gain weight more rapidly than controls reaching body weights similar to controls by 1 - 3 months after treatment

homeostasis/metabolism

decreased dopamine level ( J:110806 )

• 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

Genotype
MGI:4414756

cx3

• Allelic Composition: Dbh^tm2(Th)Rpa/Dbh⁺; Th^tm5Rpa/Th^tm5Rpa
• Genetic Background: involves: 129S4/SvJaeSor

behavior/neurological

abnormal avoidance learning behavior ( J:154773 )

• conditioned place aversion to the KOR agonist U50,488 is slightly but significantly increased compared to littermate controls

homeostasis/metabolism

decreased dopamine level ( J:154773 )

Genotype
MGI:3654638

cx4

• Allelic Composition: Dbh^tm2(Th)Rpa/Dbh⁺; Th^tm5Rpa/Th^tm5Rpa
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

mortality/aging

premature death ( J:110806 )

• without viral cre injection, phenotype is stated to be indistinguishable from mice homozygous for Th^tm1Rpa and heterozygous for Dbh^tm2(Th)Rpa

• mice die within 3 days of stopping L-DOPA treatment

behavior/neurological

aphagia ( J:110806 )

• in the absence of L-DOPA treatment

decreased locomotor activity ( J:110806 )

• severely hypoactive

bradykinesia ( J:110806 )

growth/size/body

decreased body weight ( J:110806 )

weight loss ( J:110806 )

• cessation of L-DOPA treatment results in weight loss

homeostasis/metabolism

decreased dopamine level ( J:110806 )

• dopamine levels are 0.56% of controls

• dopamine metabolite levels are also reduced

• evoked dopamine release in caudate putamen sections is absent

Genotype
MGI:2175827

cx5

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

mortality/aging

premature death ( J:30404 )

• all die by 4 weeks of age

• twice daily treatment with 50 mg/kg L-dihydroxyphenylalanine (L-DOPA) starting around P15 rescues the lethality

growth/size/body

decreased body size ( J:30404 )

• at P10 - P15

decreased body weight ( J:30404 )

• at P16, body weight is 70% of control littermates

weight loss ( J:30404 )

• 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

behavior/neurological

adipsia ( J:30404 )

• injection with L-DOPA restores drinking behavior

aphagia ( J:30404 )

• 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

poor grooming ( J:30404 )

• at P10 - P15

hunched posture ( J:30404 )

• at P10 - P15

decreased locomotor activity ( J:30404 )

• 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

decreased stereotypic behavior ( J:30404 )

• make about 280 stereotypical beam breaks per hour compared to about 700 per hour for controls

nervous system

decreased brain size ( J:30404 )

• brain size is reduced and neurons are slightly more compact; however, dopaminergic neuron and striatum morphology are similar to controls

abnormal nervous system physiology ( J:30404 )

• expression levels of tachykinin 1 and dynorphin are decreased in the striatum

homeostasis/metabolism

decreased dopamine level ( J:30404 )

• dopamine levels in the brain are low; however, levels of norepinephrine in the brain, heart, salivary glands, and adrenal glands are similar to controls

Genotype
MGI:3654636

cx6

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

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