Mouse Genome Informatics
hm1
    Ube3atm1Alb/Ube3atm1Alb
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• surviving mice are often growth-retarded

behavior/neurological
• mice demonstrate hindlimb clasping when lifted by tail
• mice often exhibit stationary posture when lifted by tail
• surviving mice are less active than littermates
• 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
• 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


Mouse Genome Informatics
hm2
    Ube3atm1Alb/Ube3atm1Alb
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• Background Sensitivity: slight reduction in survival prior to weaning compared to wild-type

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

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

reproductive system
• mammary gland development in ovarectomized females treated with progesterone and estradiol to mimic pregnance was comparable to wild-type at 12 and 14 weeks (J:99980)
• some females show increased ductal branching and lobuloalveolar development compared to wild-type controls, but penetrance of this phenotype is not consistent (J:99980)
• ovaries from 3-week old females treated with PMSG and hCG have fewer developing follicles (J:99980)
• at 8-10 weeks of age, ovaries weigh ~30% less than wild-type ovaries; at later time points, difference is not observed (J:99980)
• prostate gland weight is lower in castrated mutants treated with testosterone, compared to control castrated males treated with testosterone (J:99980)
• in 12 week old mice, testis weight is reduced by ~24% compared to wild-type (J:99980)
• uterine wet weight is ~35% lower in mutant ovarectomized females after estradiol treament compared to matched controls (J:99980)
• oocyte numbers are~68% less in 3 week old homozygous females treated with PMSG and hCG (J:99980)
• epididymal sperm counts are ~38% lower than in wild-type males (J:99980)
• ovaries from 3-week old females treated with PMSG and hCG are relatively deficient in luteinized cells (J:99980)
• female are subfertile (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
• total number of offspring sired by homozygous males with wild-type females is reduced compared to wild-type males (J:99980)
• sperm has lower ability to penetrate oocytes in vitro compared to controls (J:99980)

endocrine/exocrine glands
• mammary gland development in ovarectomized females treated with progesterone and estradiol to mimic pregnance was comparable to wild-type at 12 and 14 weeks (J:99980)
• some females show increased ductal branching and lobuloalveolar development compared to wild-type controls, but penetrance of this phenotype is not consistent (J:99980)
• ovaries from 3-week old females treated with PMSG and hCG have fewer developing follicles (J:99980)
• at 8-10 weeks of age, ovaries weigh ~30% less than wild-type ovaries; at later time points, difference is not observed (J:99980)
• prostate gland weight is lower in castrated mutants treated with testosterone, compared to control castrated males treated with testosterone (J:99980)
• in 12 week old mice, testis weight is reduced by ~24% compared to wild-type (J:99980)

integument
• mammary gland development in ovarectomized females treated with progesterone and estradiol to mimic pregnance was comparable to wild-type at 12 and 14 weeks (J:99980)
• some females show increased ductal branching and lobuloalveolar development compared to wild-type controls, but penetrance of this phenotype is not consistent (J:99980)


Mouse Genome Informatics
ht3
    Ube3atm1Alb/Ube3a+
involves: 129S7/SvEvBrd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• occasionally observed in mice with maternal deficiency

nervous system
• 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
• occasionally observed in mice with maternal deficiency


Mouse Genome Informatics
ht4
    Ube3atm1Alb/Ube3a+
involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• 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

behavior/neurological
• mice with maternal deficiency show deficits in context-dependent fear conditioning compared to littermates
• 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
• mice with maternal deficiency cannot stay on rotating rod as long as wild-type (37.9 sec vs 72.3 sec)
• 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)
• 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
• occasionally observed in mice with maternal deficiency
• longer abnormal EEG episodes in mice with maternal deficiency are accompanied by behavioral immobility which is characteristic of absence seizures

nervous system
• 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
• occasionally observed in mice with maternal deficiency
• longer abnormal EEG episodes in mice with maternal deficiency are accompanied by behavioral immobility which is characteristic of absence seizures
• reduced in weight in mice at 18 days through 4 months of age with maternal deficiency
• reduced in weight at 18 days through 4 months of age in mice with maternal deficiency
• 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
• 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
• 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
• inheritance of the maternal Ube3atm1Alb 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
OMIM IDRef(s)
Angelman Syndrome; AS 105830 J:50811


Mouse Genome Informatics
ht5
    Ube3atm1Alb/Ube3a+
involves: 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• mice with maternal deficiency (inheriting the null allele from the mother) exhibit increased epinephrine levels in the midbrain
• mice with maternal deficiency exhibit increased dopamine levels in the striatum and cortex
• DOPAC levels are increased in the striatum and midbrain
• mice with maternal deficiency exhibit increased 5HT (serotonin) levels in the frontal cortex and striatum

nervous system
• mice with maternal deficiency exhibit increased dopamine levels in the striatum and cortex
• DOPAC levels are increased in the striatum and midbrain

Mouse Models of Human Disease
OMIM IDRef(s)
Angelman Syndrome; AS 105830 J:190050