Phenotypes associated with this allele

• Allele Symbol: Drd1⁺
• Allele Name: wild type
• Allele ID: MGI:2432599
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Drd1^tm1.1(IL2RA/Venus)Koba/Drd1^+	B6.129S6-Drd1^tm1.1(IL2RA/Venus)Koba	MGI:5427828
ht2	Drd1^tm2Jcd/Drd1^+	either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * CD-1)	MGI:3709750
ht3	Drd1^tm1Jcd/Drd1^+	involves: 129S4/SvJae	MGI:3621563
cn4	Drd1^tm2Jcd/Drd1^+ Tg(EIIa-cre)C5379Lmgd/0	involves: 129S4/SvJae * BALB/c * CD-1 * FVB/N	MGI:3709752
cn5	Drd1^tm2Jcd/Drd1^+ Tg(Camk2a-cre)2Gsc/0	involves: 129S4/SvJae * FVB/N	MGI:3709758
cn6	Drd1^tm1(cre)Rpa/Drd1^+ Gad1^tm1Rpa/Gad1^tm1.1Rpa	involves: 129S4/SvJaeSor * C57BL/6	MGI:3806595
cn7	Prkar2b^tm3Gsm/Prkar2b^tm2Gsm Drd1^tm1(cre)Rpa/Drd1^+	involves: C57BL/6	MGI:5515336
cx8	Drd1^tm1Jcd/Drd1^+ Drd2^tm1Ebo/Drd2^tm1Ebo	involves: 129S2/SvPas * 129S4/SvJae * C57BL/6	MGI:4441067

Genotype
MGI:5427828

ht1

• Allelic Composition: Drd1^{tm1.1(IL2RA/Venus)Koba}/Drd1⁺
• Genetic Background: B6.129S6-Drd1^{tm1.1(IL2RA/Venus)Koba}

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

behavior/neurological

behavior/neurological phenotype ( J:184374 )

N • immunotoxin-injected mice exhibit normal spontaneous locomotion, motor learning and motivational behavior

abnormal operant conditioning behavior ( J:184374 )

• in a two-choice reaction time task dependent on light stimulus, immunotoxin-injected mice exhibit lengthened motor response compared with wild-type mice

• however, accuracy is normal

nervous system

abnormal neuron morphology ( J:184374 )

• following unilateral injection of immunotoxin, mice exhibit a loss DRD1A- and preprotachykinin-A (PPTA/TAC1)-containing neurons restricted to the dorsal region of the striatum

Genotype
MGI:3709750

ht2

• Allelic Composition: Drd1^tm2Jcd/Drd1⁺
• Genetic Background: either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * CD-1)

normal phenotype

no abnormal phenotype detected ( J:120582 )

• mice do not exhibit myoclonic jerks, dystonia or locomoter retardation, survive to a normal age, and are fertile

Genotype
MGI:3621563

ht3

• Allelic Composition: Drd1^tm1Jcd/Drd1⁺
• Genetic Background: involves: 129S4/SvJae

behavior/neurological

abnormal passive avoidance behavior ( J:67395 )

• after confinement for 1 minute to the shock-paired chamber, 3 to 5 month old heterozygous mice show less of a decline in latency to enter the conditioning chamber compared to wild-type

abnormal contextual conditioning behavior ( J:67395 )

• 3-5 month old mice exhibit delayed extinction of conditioned fear responses compared to wild-type; mice display normal acquisition of contextual fear conditioning; null mice do not show a decline in freeaing responses over three days as do the wild-type; a significantly higher her percentage of contextual freezing responses is observed for up to 90 days

Genotype
MGI:3709752

cn4

• Allelic Composition: Drd1^tm2Jcd/Drd1⁺; Tg(EIIa-cre)C5379Lmgd/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * CD-1 * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:120582 )

• at P2 mice have a small or absent milk spot and most die during the first postnatal week with some surviving to P19

nervous system

gliosis ( J:120582 )

• increase in reactive gliosis in the lateral stratum and along the corpus callosum

decreased brain size ( J:120582 )

• at P4

decreased brain weight ( J:120582 )

• at P4

abnormal forebrain morphology ( J:120582 )

• some distortion in the normal relationship of the forebrain and hippocampus

• islands of Calleja are absent

decreased forebrain size ( J:120582 )

decreased forebrain volume ( J:120582 )

• forebrain is smaller and volumetrically reduced by about 40% in the striatum with no change in cortical thickness

abnormal striatum morphology ( J:120582 )

• hypercellular stratum with frequent condensed nuclear bodies

• mice have an increase apoptotic striatum cells

abnormal hippocampus morphology ( J:120582 )

• some distortion in the normal relationship of the forebrain and hippocampus

• hippocampus is displayed anteriorly

abnormal nervous system physiology ( J:120582 )

• neuropeptides substance P and dynorphin are absent

myoclonus ( J:120582 )

• falls are more myoclonic jerks than ataxia and are sometimes locomotor-activated

• at less than P6, all mice exhibit myoclonic jerks compared to 2 of 11 normal mice

behavior/neurological

impaired righting response ( J:120582 )

• mice fail to right after spontaneous falls

dystonia ( J:120582 )

• mice display peripheral dystonia that contributes to some falls

impaired balance ( J:120582 )

• frequent falls at P2 some due to dystonia while other falls are erratic, violent, intrusive and associated with attempted movement or tactile stimulation

• falls are more myoclonic jerks than ataxia

abnormal posture ( J:120582 )

• mice have an abnormal posture when at rest

bradykinesia ( J:120582 )

myoclonus ( J:120582 )

• falls are more myoclonic jerks than ataxia and are sometimes locomotor-activated

• at less than P6, all mice exhibit myoclonic jerks compared to 2 of 11 normal mice

muscle

dystonia ( J:120582 )

• mice display peripheral dystonia that contributes to some falls

myoclonus ( J:120582 )

• falls are more myoclonic jerks than ataxia and are sometimes locomotor-activated

• at less than P6, all mice exhibit myoclonic jerks compared to 2 of 11 normal mice

respiratory system

decreased pulmonary respiratory rate ( J:120582 )

• at P2 mice exhibit periodic breathing that is resolved in older pups

cellular

gliosis ( J:120582 )

• increase in reactive gliosis in the lateral stratum and along the corpus callosum

Genotype
MGI:3709758

cn5

• Allelic Composition: Drd1^tm2Jcd/Drd1⁺; Tg(Camk2a-cre)2Gsc/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

nervous system

abnormal nervous system morphology ( J:120070 )

astrocytosis ( J:120070 )

• astrocytes had a reactive astrocyte morphology with large cell bodies and complex ramified cellular processes

• the number of reactive astrocytes (GFAP+) increases over time with a 20-fold higher number of GFAP+ cells at 9 weeks, then reduces at later time points but always remains high than in controls

• reactive astrocytes are seen in the hippocampus and cortex

decreased brain size ( J:120070 )

• after 4 weeks, approximately 12% smaller width of the entire brain compared to controls

decreased brain weight ( J:120070 )

• at 34 weeks brains weigh 15% less than wild-type

abnormal forebrain morphology ( J:120070 )

enlarged lateral ventricles ( J:120070 )

• striatal atrophy and secondary enlargement of the lateral ventricles are observed at 4 weeks in 1 mouse and in another 5 at 6 weeks

decreased striatum size ( J:120070 )

• dramatic reduction in striatal size in the second month

• striatal volume is decreased by 60% with a 65% loss in cell numbers and 17% reduction in cell density

striatum atrophy ( J:120070 )

• striatal atrophy and secondary enlargement of the lateral ventricles are observed at 4 weeks in 1 mouse and in another 5 at 6 weeks

abnormal dentate gyrus morphology ( J:120070 )

• decrease in dentate gyrus cell number

decreased hippocampus volume ( J:120070 )

• hippocampus volume is decreased

abnormal cerebral cortex morphology ( J:120070 )

• cortex volume is significantly decreased without a change in cell density or total cell number

• cortical thickness is decreased at 4,6, 8 and 30 weeks

abnormal nervous system physiology ( J:120070 )

seizures ( J:120070 )

• at 5 weeks, handling-induced seizures occur

• spontaneous seizures were recorded in 2 of 5 mice

abnormal microglial cell physiology ( J:120070 )

• activated microglia (CD11b+) are present in the cortex, hippocampus, thalamus and caudate putamen at 3 weeks but numbers decrease over time

• at 5 weeks less microglial reactivity is seen in the thalamus and no activated microglia are seen in the cortex or hippocampus

• at 21 weeks mice are free of microglia

abnormal interictal brain wave pattern ( J:120070 )

• interictal electroencephalogram (EEG) is abnormal

behavior/neurological

limb grasping ( J:120070 )

• at 4 weeks, hindlimb clasping is subtle

• at 12 weeks, frequent paroxysmal bursts of dystonic hindlimb retraction are observed

• at 14 weeks, mice sustain hindlimb clasping with trunk flexion

dystonia ( J:120070 )

• at 12 weeks, frequent paroxysmal bursts of dystonic hindlimb retraction are observed

trunk curl ( J:120070 )

• at 14 weeks trunk flexion associated with hindlimb clasping

increased vertical activity ( J:120070 )

• at 6 to 9 weeks and 16 to 21 weeks, there is a decrease in chewing and shifting while total rearing is increased

increased locomotor activity ( J:120070 )

• at 6 to 9 weeks but not at 16 to 21 weeks, mice show increases in distance covered, time spent moving and speed of movement

• increase in sniffing

seizures ( J:120070 )

• at 5 weeks, handling-induced seizures occur

• spontaneous seizures were recorded in 2 of 5 mice

muscle

dystonia ( J:120070 )

• at 12 weeks, frequent paroxysmal bursts of dystonic hindlimb retraction are observed

growth/size/body

decreased body weight ( J:120070 )

• males and females weigh 17% and 25%, respectively, less than wild-type

immune system

abnormal microglial cell physiology ( J:120070 )

• activated microglia (CD11b+) are present in the cortex, hippocampus, thalamus and caudate putamen at 3 weeks but numbers decrease over time

• at 5 weeks less microglial reactivity is seen in the thalamus and no activated microglia are seen in the cortex or hippocampus

• at 21 weeks mice are free of microglia

hematopoietic system

abnormal microglial cell physiology ( J:120070 )

• activated microglia (CD11b+) are present in the cortex, hippocampus, thalamus and caudate putamen at 3 weeks but numbers decrease over time

• at 5 weeks less microglial reactivity is seen in the thalamus and no activated microglia are seen in the cortex or hippocampus

• at 21 weeks mice are free of microglia

cellular

astrocytosis ( J:120070 )

• astrocytes had a reactive astrocyte morphology with large cell bodies and complex ramified cellular processes

• the number of reactive astrocytes (GFAP+) increases over time with a 20-fold higher number of GFAP+ cells at 9 weeks, then reduces at later time points but always remains high than in controls

• reactive astrocytes are seen in the hippocampus and cortex

abnormal microglial cell physiology ( J:120070 )

• activated microglia (CD11b+) are present in the cortex, hippocampus, thalamus and caudate putamen at 3 weeks but numbers decrease over time

• at 5 weeks less microglial reactivity is seen in the thalamus and no activated microglia are seen in the cortex or hippocampus

• at 21 weeks mice are free of microglia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:120070

Genotype
MGI:3806595

cn6

• Allelic Composition: Drd1^tm1(cre)Rpa/Drd1⁺; Gad1^tm1Rpa/Gad1^tm1.1Rpa
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:138586 )

N • mice exhibit normal gait and response to the Drd1a agonist SKF81297

limb grasping ( J:138586 )

abnormal motor coordination/balance ( J:138586 )

• mice spend more time on a rotarod than heterozygous controls

decreased grip strength ( J:138586 )

• on the second of three trials mice exhibit decreased strength in a modified wire hang test compared to heterozygous controls

Genotype
MGI:5515336

cn7

• Allelic Composition: Prkar2b^tm3Gsm/Prkar2b^tm2Gsm; Drd1^tm1(cre)Rpa/Drd1⁺
• Genetic Background: involves: C57BL/6

behavior/neurological

hyperactivity ( J:196157 )

• remain hyperactive

growth/size/body

growth/size/body region phenotype ( J:196157 )

N • body weight similar to controls

adipose tissue

adipose tissue phenotype ( J:196157 )

N • adiposity similar to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:196157 )

N • serum leptin levels similar to controls

Genotype
MGI:4441067

cx8

• Allelic Composition: Drd1^tm1Jcd/Drd1⁺; Drd2^tm1Ebo/Drd2^tm1Ebo
• Genetic Background: involves: 129S2/SvPas * 129S4/SvJae * C57BL/6

mortality/aging

mortality/aging ( J:91781 )

N • mutant mice are viable and able to reach adulthood