Phenotypes Associated with This Genotype

Genotype
MGI:3694359

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

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

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