Phenotypes associated with this allele

• Allele Symbol: Th^tm5Rpa
• Allele Name: targeted mutation 5, Richard D Palmiter
• Allele ID: MGI:3527166
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Th^tm5Rpa/Th^tm5Rpa	involves: 129S4/SvJaeSor * C57BL/6	MGI:3711316
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

Genotype
MGI:3711316

hm1

• Allelic Composition: Th^tm5Rpa/Th^tm5Rpa
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

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

mortality/aging

prenatal lethality, complete penetrance ( J:110806 )

• no homozygotes are found at birth

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