Phenotypes associated with this allele

• Allele Symbol: Ube3a⁺
• Allele Name: wild type
• Allele ID: MGI:2433456
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Ube3a^tm1Jwf/Ube3a^+	B6.129S4-Ube3a^tm1Jwf	MGI:3852128
ht2	Ube3a^em1Mjz/Ube3a^+	C57BL/6J-Ube3a^em1Mjz	MGI:7520328
ht3	Ube3a^em1(IMPC)Hmgu/Ube3a^+	C57BL/6N-Ube3a^em1(IMPC)Hmgu/Ieg	MGI:6408750
ht4	Ube3a^tm1Yelg/Ube3a^+	involves: 129P2/OlaHsd * 129S2/SvPasCrl	MGI:5704111
ht5	Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd	MGI:3694362
ht6	Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3694359
ht7	Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd * C57BL/6J	MGI:5461654
cn8	Ube3a^tm1.1Bdph/Ube3a^+ 7630403G23Rik^Tg(Th-cre)1Tmd/7630403G23Rik^+	B6.Cg-Ube3a^tm1.1Bdph 7630403G23Rik^Tg(Th-cre)1Tmd	MGI:5882094
cn9	Tg(CAG-cre)13Miya/0 Ube3a^tm1Yelg/Ube3a^+	involves: 129P2/OlaHsd * 129S2/SvPasCrl * C57BL/6J	MGI:5704116
cn10	Tg(CAG-cre/Esr1*)5Amc/0 Ube3a^tm1Yelg/Ube3a^+	involves: 129P2/OlaHsd * 129S2/SvPasCrl * C57BL/6J	MGI:5704117
cx11	Snhg14^tm1Alb/Snhg14^+ Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:5587829

Genotype
MGI:3852128

ht1

• Allelic Composition: Ube3a^tm1Jwf/Ube3a⁺
• Genetic Background: B6.129S4-Ube3a^tm1Jwf

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

behavior/neurological

abnormal learning/memory/conditioning ( J:102546 )

impaired contextual conditioning behavior ( J:75622 )

• when this allele is inherited maternally, mice exhibit less freezing 24 hours after contextual fear conditioning compared to similarly treated wild-type mice

abnormal spatial learning ( J:75622 )

• when the allele is inherited maternally, mice exhibit impaired performance in a Morris water maze compared with wild-type mice

abnormal motor capabilities/coordination/movement ( J:102546 )

impaired coordination ( J:75622 )

• when the allele is inherited maternally, mice exhibit impaired performance on a rotarod compared with wild-type mice

abnormal posture ( J:102546 )

• when this allele is inherited maternally during waking periods when cortical bursts are observed unlike in wild-type mice

decreased locomotor activity ( J:102546 )

• when this allele is inherited maternally during waking periods when cortical bursts are observed unlike in wild-type mice

abnormal sleep pattern ( J:102546 )

• when this allele is inherited maternally, mice exhibit increased waking and slow-wave sleep episode numbers compared to in wild-type mice

• when this allele is inherited maternally, mice exhibit reduced duration of slow-wave sleep episodes with increased waking at the dark/light transition compared with wild-type mice

• when this allele is inherited maternally, mice exhibit less of an increase in the amount of paradoxical sleep and unchanged slow-wave sleep amounts during recovery after a 4-hour sleep deprivation compared with wild-type mice

abnormal spike wave discharge ( J:75622 , J:95305 , J:102546 )

• 6 of 8 mice exhibit intermittent bursts of 4 to 5 Hz spike-wave discharged lasting 5 to 12 seconds unlike wild-type mice (J:75622)

• spike-wave discharges occur at variable frequencies, typically every 2 to 3 minutes, without behavior change (J:75622)

• 2 mice exhibited electrographic seizures without behavior change (J:75622)

• when this allele is inherited maternally, Purkinje cell simple spike spontaneous firing rate is higher than in wild-type mice (J:95305)

• however, spontaneous complex spike firing rate is normal (J:95305)

• when this allele is inherited maternally, one-sided peak counts of simple spike autocorrelogram are higher than in wild-type mice (J:95305)

• when this allele is inherited maternally, the rhythm index is higher than in wild-type mice (J:95305)

• when this allele is inherited maternally, mice exhibit spike-wave discharges during wake and slow-wave sleep periods unlike wild-type mice (J:102546)

nervous system

abnormal spike wave discharge ( J:75622 , J:95305 , J:102546 )

• 6 of 8 mice exhibit intermittent bursts of 4 to 5 Hz spike-wave discharged lasting 5 to 12 seconds unlike wild-type mice (J:75622)

• spike-wave discharges occur at variable frequencies, typically every 2 to 3 minutes, without behavior change (J:75622)

• 2 mice exhibited electrographic seizures without behavior change (J:75622)

• when this allele is inherited maternally, Purkinje cell simple spike spontaneous firing rate is higher than in wild-type mice (J:95305)

• however, spontaneous complex spike firing rate is normal (J:95305)

• when this allele is inherited maternally, one-sided peak counts of simple spike autocorrelogram are higher than in wild-type mice (J:95305)

• when this allele is inherited maternally, the rhythm index is higher than in wild-type mice (J:95305)

• when this allele is inherited maternally, mice exhibit spike-wave discharges during wake and slow-wave sleep periods unlike wild-type mice (J:102546)

decreased brain weight ( J:75622 )

• at 2 and 5 weeks when the allele is inherited maternally

• however, brain morphology is otherwise normal

abnormal nervous system electrophysiology ( J:95305 )

• when this allele is inherited maternally, mice exhibit spontaneous spindle-shaped local field potential oscillations throughout the vermis, uvula, and nodulus unlike wild-type mice

• when this allele is inherited maternally, mice exhibit highly rhythmic firing in 50% of Purkinje cells unlike in wild-type cells

abnormal brain wave pattern ( J:102546 )

• when this allele is inherited maternally, mice exhibit no changes in delta waves during slow-wave sleep and theta waves during paradocical sleep while recovering from a 4-hour sleep deprivation unlike wild-type mice

abnormal brain theta wave pattern ( J:102546 )

• when this allele is inherited maternally, theta peak frequency is increased during paradoxical sleep compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Angelman syndrome		DOID:1932	OMIM:105830	J:75622

Genotype
MGI:7520328

ht2

• Allelic Composition: Ube3a^em1Mjz/Ube3a⁺
• Genetic Background: C57BL/6J-Ube3a^em1Mjz

behavior/neurological

behavior/neurological phenotype ( J:338299 )

N • normal time rearing in open field test if maternal or paternal allele inherited

abnormal motor learning ( J:338299 )

• longer latency to fall in accelerating rotarod test if maternal allele inherited

• normal latency to fall in accelerating rotarod test if paternal allele inherited

decreased thigmotaxis ( J:338299 )

• more time spent in center in open field test at age 50 weeks if maternal allele inherited

• normal time spent in center in open field test at age up to 44 weeks if maternal allele inherited

• normal behavior in open field test if paternal allele inherited

increased locomotor activity ( J:338299 )

• increased distance traveled in open field test if maternal allele inherited

• increased entry times in three-chamber test if maternal allele inherited

• normal behavior in open field test if paternal allele inherited

• normal entry times in three-chamber test if paternal allele inherited

decreased social investigation ( J:338299 )

• no preference for unfamiliar mouse in three-chamber test if paternal allele inherited

• normal preference for unfamiliar mouse in three-chamber test if maternal allele inherited

embryo

embryo phenotype ( J:338299 )

N • mice born at normal Mendelian ratios

growth/size/body

growth/size/body region phenotype ( J:338299 )

N • normal body weight

nervous system

nervous system phenotype ( J:338299 )

N • normal brain weight and cortical thickness, organization and excitatory neuron numbers

Genotype
MGI:6408750

ht3

• Allelic Composition: Ube3a^{em1(IMPC)Hmgu}/Ube3a⁺
• Genetic Background: C57BL/6N-Ube3a^{em1(IMPC)Hmgu}/Ieg

Data Sources

IMPC Data for Ube3a

behavior/neurological

decreased food intake ( J:211773 )

♂

IMPC - HMGU

decreased locomotor activity ( J:211773 )

IMPC - HMGU

hematopoietic system

increased hematocrit ( J:211773 )

IMPC - HMGU

homeostasis/metabolism

decreased respiratory quotient ( J:211773 )

♂

IMPC - HMGU

Genotype
MGI:5704111

ht4

• Allelic Composition: Ube3a^tm1Yelg/Ube3a⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPasCrl

cellular

paternal imprinting ( J:222400 )

• this allele is maternally inherited and silenced in males by imprinting

behavior/neurological

abnormal emotion/affect behavior ( J:222400 )

• mice with a maternally inherited allele exhibit alterations in marble burying, showing a higher number of unburied marbles than controls

abnormal depression-related behavior ( J:222400 )

• mice inheriting the mutant allele from the mother exhibit alterations in the forced swim test, showing increased floating time compared to controls

impaired coordination ( J:222400 )

• mice inheriting the mutant allele from the mother exhibit alterations in rotarod performance, showing shorter latencies to fall off the rod

decreased locomotor activity ( J:222400 )

• mice with a maternally inherited allele exhibit alterations in open field explorations, showing shorter path lengths than controls

abnormal nest building behavior ( J:222400 )

• mice with a maternally inherited allele exhibit alterations in nest building; the percent of used nesting is lower in mutants than in controls indicating decreased nest building

audiogenic seizures ( J:222400 )

• mice with a maternally inherited allele exhibit alterations in audiogenic seizure threshold, showing a large increase in mice with seizures

• treatment of adults with either valproate or clonazepam for 5 days prevents audiogenic seizures

nervous system

audiogenic seizures ( J:222400 )

• mice with a maternally inherited allele exhibit alterations in audiogenic seizure threshold, showing a large increase in mice with seizures

• treatment of adults with either valproate or clonazepam for 5 days prevents audiogenic seizures

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Angelman syndrome		DOID:1932	OMIM:105830	J:222400

Genotype
MGI:3694362

ht5

• Allelic Composition: Ube3a^tm1Alb/Ube3a⁺
• Genetic Background: involves: 129S7/SvEvBrd

behavior/neurological

audiogenic seizures ( J:50811 )

• Background Sensitivity: observed in 18% of mice with paternal deficiency and 85% (17/20) with maternal deficiency compared to mice on 129/B6 background

• mice with maternal deficiency are susceptible to audiogenic seizures characterized by running and leaping followed by tonic clonic seizures

tonic-clonic seizures ( J:50811 )

• occasionally observed in mice with maternal deficiency

nervous system

audiogenic seizures ( J:50811 )

• Background Sensitivity: observed in 18% of mice with paternal deficiency and 85% (17/20) with maternal deficiency compared to mice on 129/B6 background

• mice with maternal deficiency are susceptible to audiogenic seizures characterized by running and leaping followed by tonic clonic seizures

tonic-clonic seizures ( J:50811 )

• occasionally observed in mice with maternal deficiency

Genotype
MGI:3694359

ht6

• Allelic Composition: Ube3a^tm1Alb/Ube3a⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

growth/size/body

decreased body weight ( J:50811 )

• mice with maternal Ube3a deficiency (inheriting null allele from mother) have significant reduction in body weight at 18 days of age; by 4 months, difference is gone

increased body weight ( J:207499 )

• starting at 3 months when this allele is inherited maternally

behavior/neurological

abnormal contextual conditioning behavior ( J:50811 )

• mice with maternal deficiency show deficits in context-dependent fear conditioning compared to littermates

impaired contextual conditioning behavior ( J:207499 )

• reduced freezing when this allele is inherited maternally

abnormal motor learning ( J:50811 )

• mice with maternal deficiency exhibit impaired motor learning in accelerating rod test, staying on apparatus for significantly less time (193 sec) than wild-type (439 sec) on first day; by day 4, time difference was not significant

abnormal emotion/affect behavior ( J:207499 )

• impaired performance in a marble burying test when this allele is inherited maternally

impaired coordination ( J:50811 , J:207499 )

• mice with maternal deficiency cannot stay on rotating rod as long as wild-type (37.9 sec vs 72.3 sec) (J:50811)

• on an accelerating rotarod, wire hang test and dowel test when this allele is inherited maternally (J:207499)

abnormal gait ( J:50811 )

• mice with maternal deficiency have shorter step distance (5 cm) and reduced left-right step alternation coefficient (0.08) compared to wild-type littermates(5.9 cm, 0.14)

decreased locomotor activity ( J:207499 )

• when this allele is inherited maternally

audiogenic seizures ( J:50811 )

• Background Sensitivity: observed in 20-30% of mice with maternal deficiency on hybrid background

• mice with maternal deficiency are substantially more susceptible to audiogenic seizures characterized by running and leaping followed by tonic clonic seizures

tonic-clonic seizures ( J:50811 )

• occasionally observed in mice with maternal deficiency

absence seizures ( J:50811 )

• longer abnormal EEG episodes in mice with maternal deficiency are accompanied by behavioral immobility which is characteristic of absence seizures

nervous system

audiogenic seizures ( J:50811 )

• Background Sensitivity: observed in 20-30% of mice with maternal deficiency on hybrid background

• mice with maternal deficiency are substantially more susceptible to audiogenic seizures characterized by running and leaping followed by tonic clonic seizures

tonic-clonic seizures ( J:50811 )

• occasionally observed in mice with maternal deficiency

absence seizures ( J:50811 )

• longer abnormal EEG episodes in mice with maternal deficiency are accompanied by behavioral immobility which is characteristic of absence seizures

abnormal cerebral cortex morphology ( J:50811 )

• reduced in weight in mice at 18 days through 4 months of age with maternal deficiency

small cerebellum ( J:50811 )

• reduced in weight at 18 days through 4 months of age in mice with maternal deficiency

abnormal dendrite morphology ( J:130068 )

• when inherited maternally, the dendritic spines on cerebellar Purkinje cells and hippocampal and cortical pyramidal neurons exhibit reduced spine density (1.228+/-0.055 spines per um compared to 1.614+/-0.076 spines per um in wild-type mice), a reduced number of spines along cortical apical dendrites (0.882+/-0.057 spines per um compared to 1.172+/-0.044 spines per um in wild-type mice), and reduced spine length (1.017+/-0.0454 um compared to 1.16+/-0.0038 um in wild-type mice)

• dendrites are thinner than in wild-type mice

• pyramidal dendrites exhibit varicosities along the secondary dendritic shaft unlike in wild-type mice

abnormal nervous system electrophysiology ( J:50811 )

abnormal brain wave pattern ( J:50811 )

• EEG activity is abnormal with abundant bilateral 3 sec spike activity mixed with polyspike and slow wave discharges

• longer abnormal EEG episodes in mice with maternal deficiency are accompanied by behavioral immobility which is characteristic of absence seizures

abnormal long-term potentiation ( J:207499 )

• decaying LTP when this allele is inherited maternally

reduced long-term potentiation ( J:50811 )

• hippocampal slices from mice with maternal deficiency display reduced LTP; high frequency stimulation only produces transient potentiation (short term potentiation) compared to LTP produced in wild-type

cellular

paternal imprinting ( J:50811 , J:130068 )

• inheritance of the maternal Ube3a^tm1Alb allele results in much more severe phenotypic effects compared to inheritance of the paternal allele (J:50811)

• this allele is maternally inherited and silenced in males by imprinting (J:130068)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Angelman syndrome		DOID:1932	OMIM:105830	J:50811

Genotype
MGI:5461654

ht7

• Allelic Composition: Ube3a^tm1Alb/Ube3a⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

homeostasis/metabolism

abnormal adrenaline level ( J:190050 )

• mice with maternal deficiency (inheriting the null allele from the mother) exhibit increased epinephrine levels in the midbrain

increased dopamine level ( J:190050 )

• mice with maternal deficiency exhibit increased dopamine levels in the striatum and cortex

• DOPAC levels are increased in the striatum and midbrain

increased serotonin level ( J:190050 )

• mice with maternal deficiency exhibit increased 5HT (serotonin) levels in the frontal cortex and striatum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Angelman syndrome		DOID:1932	OMIM:105830	J:190050

Genotype
MGI:5882094

cn8

• Allelic Composition: Ube3a^tm1.1Bdph/Ube3a⁺; 7630403G23Rik^{Tg(Th-cre)1Tmd}/7630403G23Rik⁺
• Genetic Background: B6.Cg-Ube3a^tm1.1Bdph 7630403G23Rik^{Tg(Th-cre)1Tmd}

behavior/neurological

abnormal operant conditioning behavior ( J:235694 )

• when the allele is inherited maternally, mice nose poke more for 30 Hz stimulation than controls, indicating enhanced motivation

nervous system

abnormal GABA-mediated receptor currents ( J:235694 )

• mice with a maternally inherited allele show a greater than 50% reduction in peak amplitude of GABAergic currents relative to controls, while current decay kinetics are normal, indicating decreased GABA co-release

• mice with a maternally inherited allele exhibit diminished GABAergic currents at 30 Hz stimulation of ventral tegmental area-to-nucleus accumbens (VTA-to-NAc) terminals compared to controls

• expression of exogenous vesicular GABA transporter (VGAT) within TH+ terminals normalizes optical intracranial self-stimulation in mice with a maternally inherited allele

• however, no changes in optically evoked dopamine release in TH+ VTA-to-NAc terminals is seen in mice with a maternally inherited allele and mice also exhibit normal glutamatergic co-release with optical stimulation of VTA-to-NAc termimals

Genotype
MGI:5704116

cn9

• Allelic Composition: Tg(CAG-cre)13Miya/0; Ube3a^tm1Yelg/Ube3a⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPasCrl * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:222400 )

N • mice with a maternally inherited allele exhibit a full rescue of neurological and behavioral abnormalities (rotarod, marble burying, open field explorations, nest building, audiogenic seizure threshold, and forced swim test)

Genotype
MGI:5704117

cn10

• Allelic Composition: Tg(CAG-cre/Esr1*)5Amc/0; Ube3a^tm1Yelg/Ube3a⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPasCrl * C57BL/6J

behavior/neurological

abnormal emotion/affect behavior ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in marble burying, indicating no rescue of this phenotype when gene expression is re-established at those times

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams does not rescue the deficits in marble burying

abnormal depression-related behavior ( J:222400 )

• mice treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in the forced swim test, indicating no rescue of this phenotype

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams does not rescue the deficits in the forced swim test

impaired coordination ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 14 weeks (adults) do not show any rescue of motor coordination deficit at 28 weeks of age

• however, mice with a maternally inherited allele treated with tamoxifen at 6 weeks (adolescents) show partial rescue of motor coordination deficit at 22 weeks of age and mice treated with tamoxifen at 3 weeks (juveniles) show full rescue of motor coordination deficit at 16 weeks of age

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams rescues fully the motor coordination deficit

decreased locomotor activity ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in the open field explorations, indicating no rescue of this phenotype

• however, tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams results in improved performance in the open field

abnormal nest building behavior ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3, 6, or 14 weeks of age show alterations in nest building, indicating no rescue of this phenotype

• tamoxifen treatment of mice with a maternally inherited allele immediately after birth via administration to lactating dams does not rescue the deficits in nest building

audiogenic seizures ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3 weeks of age show increased audiogenic seizure threshold, indicating no rescue of this phenotype

nervous system

audiogenic seizures ( J:222400 )

• mice with a maternally inherited allele treated with tamoxifen at 3 weeks of age show increased audiogenic seizure threshold, indicating no rescue of this phenotype

abnormal long-term potentiation ( J:222400 )

• mice with a maternally inherited allele not treated with tamoxifen exhibit abnormal Schaffer collateral-CA1 long term potentiation indicating a hippocampal plasticity deficit

• mice with a maternally inherited allele show full recovery of hippocampal LTP when treated with tamoxifen at 3 and 14 weeks of age

Genotype
MGI:5587829

cx11

• Allelic Composition: Snhg14^tm1Alb/Snhg14⁺; Ube3a^tm1Alb/Ube3a⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:207499 )

N • when the knock-out allele is inherited maternally, mice exhibit fully restored contextual conditioning behavior compared with mice heterozygous for the wild-type allele

abnormal emotion/affect behavior ( J:207499 )

• when the knock-out allele is inherited maternally, mice exhibit a slight improvement in performance in a marble burying test compared with mice heterozygous for the wild-type allele

impaired coordination ( J:207499 )

• on an accelerating rotarod in later trials when the knock-out allele is inherited maternally

• however, performance improved in the first few trials and in the hanging wire and dowel tests

decreased locomotor activity ( J:207499 )

• when the knock-out allele is inherited maternally, mice exhibit a trend towards improved activity levels compared with mice heterozygous for the wild-type allele

growth/size/body

growth/size/body region phenotype ( J:207499 )

N • when the knock-out allele is inherited maternally, mice exhibit normal body weight unlike in mice heterozygous for the wild-type allele

nervous system

nervous system phenotype ( J:207499 )

N • when the knock-out allele is inherited maternally, mice exhibit restored long term potentiation compared with mice heterozygous for the wild-type allele