Phenotypes associated with this allele

• Allele Symbol: Ube3a^tm1Alb
• Allele Name: targeted mutation 1, Arthur L Beaudet
• Allele ID: MGI:2181811
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ube3a^tm1Alb/Ube3a^tm1Alb	involves: 129S7/SvEvBrd	MGI:3694361
hm2	Ube3a^tm1Alb/Ube3a^tm1Alb	involves: 129S7/SvEvBrd * C57BL/6	MGI:3694360
ht3	Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd	MGI:3694362
ht4	Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:3694359
ht5	Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd * C57BL/6J	MGI:5461654
cx6	Snhg14^tm1Alb/Snhg14^+ Ube3a^tm1Alb/Ube3a^+	involves: 129S7/SvEvBrd * C57BL/6	MGI:5587829

Genotype
MGI:3694361

hm1

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

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:50811 )

• Background Sensitivity: substantial reduction in postnatal survival compared to mice on 129/B6 background, is seen, with death frequently observed during the first 48 hours postnatal (about 80%)

growth/size/body

postnatal growth retardation ( J:50811 )

• surviving mice are often growth-retarded

behavior/neurological

limb grasping ( J:50811 )

• mice demonstrate hindlimb clasping when lifted by tail

abnormal posture ( J:50811 )

• mice often exhibit stationary posture when lifted by tail

bradykinesia ( J:50811 )

• surviving mice are less active than littermates

audiogenic seizures ( J:50811 )

• Background Sensitivity: observed in all mice (5/5)

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

nervous system

audiogenic seizures ( J:50811 )

• Background Sensitivity: observed in all mice (5/5)

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

Genotype
MGI:3694360

hm2

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

mortality/aging

postnatal lethality ( J:50811 )

• Background Sensitivity: slight reduction in survival prior to weaning compared to wild-type

behavior/neurological

audiogenic seizures ( J:50811 )

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

nervous system

audiogenic seizures ( J:50811 )

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

reproductive system

decreased oocyte number ( J:99980 )

♀ • oocyte numbers are~68% less in 3 week old homozygous females treated with PMSG and hCG

oligozoospermia ( J:99980 )

♂ • epididymal sperm counts are ~38% lower than in wild-type males

abnormal mammary gland growth during pregnancy ( J:99980 )

♀ • mammary gland development in ovarectomized females treated with progesterone and estradiol to mimic pregnance was comparable to wild-type at 12 and 14 weeks

♀ • some females show increased ductal branching and lobuloalveolar development compared to wild-type controls, but penetrance of this phenotype is not consistent

decreased prostate gland weight ( J:99980 )

♂ • prostate gland weight is lower in castrated mutants treated with testosterone, compared to control castrated males treated with testosterone

abnormal ovarian folliculogenesis ( J:99980 )

♀ • ovaries from 3-week old females treated with PMSG and hCG have fewer developing follicles

decreased ovary weight ( J:99980 )

♀ • at 8-10 weeks of age, ovaries weigh ~30% less than wild-type ovaries; at later time points, difference is not observed

decreased testis weight ( J:99980 )

♂ • in 12 week old mice, testis weight is reduced by ~24% compared to wild-type

decreased uterus weight ( J:99980 )

♀ • uterine wet weight is ~35% lower in mutant ovarectomized females after estradiol treament compared to matched controls

impaired sperm capacitation ( J:99980 )

♂ • sperm has lower ability to penetrate oocytes in vitro compared to controls

impaired luteinization ( J:99980 )

♀ • ovaries from 3-week old females treated with PMSG and hCG are relatively deficient in luteinized cells

reduced female fertility ( J:99980 )

♀ • female are subfertile

decreased litter size ( J:99980 )

• litters sired by homozygous males with wild-type females have ~34% fewer pups/litter

• litter size is ~48% lower in homozygous females compared to wild-type

reduced male fertility ( J:99980 )

♂ • total number of offspring sired by homozygous males with wild-type females is reduced compared to wild-type males

endocrine/exocrine glands

abnormal mammary gland growth during pregnancy ( J:99980 )

♀ • mammary gland development in ovarectomized females treated with progesterone and estradiol to mimic pregnance was comparable to wild-type at 12 and 14 weeks

♀ • some females show increased ductal branching and lobuloalveolar development compared to wild-type controls, but penetrance of this phenotype is not consistent

decreased prostate gland weight ( J:99980 )

♂ • prostate gland weight is lower in castrated mutants treated with testosterone, compared to control castrated males treated with testosterone

abnormal ovarian folliculogenesis ( J:99980 )

♀ • ovaries from 3-week old females treated with PMSG and hCG have fewer developing follicles

decreased ovary weight ( J:99980 )

♀ • at 8-10 weeks of age, ovaries weigh ~30% less than wild-type ovaries; at later time points, difference is not observed

decreased testis weight ( J:99980 )

♂ • in 12 week old mice, testis weight is reduced by ~24% compared to wild-type

integument

abnormal mammary gland growth during pregnancy ( J:99980 )

♀ • mammary gland development in ovarectomized females treated with progesterone and estradiol to mimic pregnance was comparable to wild-type at 12 and 14 weeks

♀ • some females show increased ductal branching and lobuloalveolar development compared to wild-type controls, but penetrance of this phenotype is not consistent

cellular

decreased oocyte number ( J:99980 )

♀ • oocyte numbers are~68% less in 3 week old homozygous females treated with PMSG and hCG

oligozoospermia ( J:99980 )

♂ • epididymal sperm counts are ~38% lower than in wild-type males

Genotype
MGI:3694362

ht3

• 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

ht4

• 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

ht5

• 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:5587829

cx6

• 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