Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-App*R609D*K612E)6Vln
• Allele Name: transgene insertion 6, Fred Van Leuven
• Allele ID: MGI:3720071
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(Thy1-App*R609D*K612E)6Vln/Tg(Thy1-App*R609D*K612E)6Vln	involves: FVB	MGI:3720106
tg2	Tg(Thy1-App*R609D*K612E)6Vln/0	involves: FVB	MGI:3720105

Genotype
MGI:3720106

tg1

• Allelic Composition: Tg(Thy1-App*R609D*K612E)6Vln/Tg(Thy1-App*R609D*K612E)6Vln
• Genetic Background: involves: FVB

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

mortality/aging

premature death ( J:32213 )

• >50% of transgenic mice die by ~100 days of age compared to ~7% of nontransgenic littermates

behavior/neurological

lethargy ( J:32213 )

• following seizures, mice are lethargic for variable periods of time

abnormal response to new environment ( J:32213 )

• upon transfer to new cage, many mice show neophobia

increased aggression towards mice ( J:32213 )

• males older than 2 months display increased aggressiveness towards other males, with frequent and severe fighting

increased thigmotaxis ( J:32213 )

• significantly more (~4%) mice older than ~2 months display long latency of >5 seconds when placed in a new environment compared to 5% of control FVB mice, whereas 4-6 week old mice show similar latency to control animals

abnormal locomotor activation ( J:32213 )

• after 2 months of age, mice display increased agitation and bouts of wild running

• in open field tests, mice 6-20 weeks old display significantly reduced ambulation, with number of corner crossings skewed toward lower values relative to controls which show a Gaussian distribution

behavioral arrest ( J:32213 )

• upon transfer to new cage, many mice show postural freezing; significantly more mice 3-5 months of age display posture freezing compared to 2% of wild-type controls

seizures ( J:32213 )

• after 2 months of age, >60% of mice show mild seizures of varying severity compared to very few in transgenic mice on the C57BL background

decreased susceptibility to pharmacologically induced seizures ( J:32213 )

• less susceptible than wild-type or line 6 transgenic mice to NMDA-induced seizures and mortality at all doses of NMDA treatment, displaying no symptoms and dying only when given doses of 150mg/kg

increased susceptibility to pharmacologically induced seizures ( J:32213 )

• mice are more sensitive to kainic acid than wild-type, with all mice displaying stage 5 seizures at a dose of 40 mg/kg compared to only 30% of wild-type exhibiting stage 5 and 66% having stage 4 seizures

clonic seizures ( J:32213 )

• mice older than 6 months exhibit tonic-clonic seizures of 30-60 seconds, followed by whole body clonic seizures

myoclonus ( J:32213 )

• many mice display seizures with facial movements, mild fore-limb clonus and mild whole body clonus lasting from 5 to 10 seconds

tonic-clonic seizures ( J:32213 )

• mice older than 6 months show severe tonic-clonic seizures lasting 30-60 seconds, with gasping and stretching all four limbs out with their tail upright, followed by severe whole body clonic seizures

nervous system

seizures ( J:32213 )

• after 2 months of age, >60% of mice show mild seizures of varying severity compared to very few in transgenic mice on the C57BL background

decreased susceptibility to pharmacologically induced seizures ( J:32213 )

• less susceptible than wild-type or line 6 transgenic mice to NMDA-induced seizures and mortality at all doses of NMDA treatment, displaying no symptoms and dying only when given doses of 150mg/kg

increased susceptibility to pharmacologically induced seizures ( J:32213 )

• mice are more sensitive to kainic acid than wild-type, with all mice displaying stage 5 seizures at a dose of 40 mg/kg compared to only 30% of wild-type exhibiting stage 5 and 66% having stage 4 seizures

clonic seizures ( J:32213 )

• mice older than 6 months exhibit tonic-clonic seizures of 30-60 seconds, followed by whole body clonic seizures

myoclonus ( J:32213 )

• many mice display seizures with facial movements, mild fore-limb clonus and mild whole body clonus lasting from 5 to 10 seconds

tonic-clonic seizures ( J:32213 )

• mice older than 6 months show severe tonic-clonic seizures lasting 30-60 seconds, with gasping and stretching all four limbs out with their tail upright, followed by severe whole body clonic seizures

muscle

myoclonus ( J:32213 )

• many mice display seizures with facial movements, mild fore-limb clonus and mild whole body clonus lasting from 5 to 10 seconds

facial muscle spasm ( J:32213 )

respiratory system

abnormal respiration ( J:32213 )

• mice of all ages exhibit markedly increased respiratory rate in a new environment

Genotype
MGI:3720105

tg2

• Allelic Composition: Tg(Thy1-App*R609D*K612E)6Vln/0
• Genetic Background: involves: FVB

mortality/aging

premature death ( J:32213 )

• 44% of transgenic mice die within the first year of life, compared to 7% of nontransgenic littermates; first death occurred at 150days of age

behavior/neurological

lethargy ( J:32213 )

• following seizures, mice are lethargic for variable periods of time

abnormal response to new environment ( J:32213 )

• upon transfer to new cage, many mice show neophobia

increased thigmotaxis ( J:32213 )

• significantly more (~47%) mice older than ~2 months display long latency of >5 seconds when placed in a new environment compared to 5% of control FVB mice, whereas 4-6 week old mice show similar latency to control animals

abnormal locomotor activation ( J:32213 )

• after 3 months of age, mice display increased agitation and bouts of wild running

• in open field tests, mice 6-20 weeks old display significantly reduced ambulation, with number of corner crossings skewed toward lower values relative to controls which show a Gaussian distribution

behavioral arrest ( J:32213 )

• upon transfer to new cage, many mice show postural freezing; 23% of mice 3-5 months of age display posture freezing compared to 2% of wild-type controls

seizures ( J:32213 )

• after 3 months of age, >60% of mice show mild seizures of varying severity compared to very few in transgenic mice on the C57BL background

clonic seizures ( J:32213 )

• mice older than 6 months exhibit tonic-clonic seizures of 30-60 seconds, followed by whole body clonic seizures

myoclonus ( J:32213 )

• many mice display seizures with facial movements, mild fore-limb clonus and mild whole body clonus lasting from 5 to 10 seconds

tonic-clonic seizures ( J:32213 )

• mice older than 6 months show severe tonic-clonic seizures lasting 30-60 seconds, with gasping and stretching all four limbs out with their tail upright, followed by severe whole body clonic seizures

nervous system

seizures ( J:32213 )

• after 3 months of age, >60% of mice show mild seizures of varying severity compared to very few in transgenic mice on the C57BL background

clonic seizures ( J:32213 )

• mice older than 6 months exhibit tonic-clonic seizures of 30-60 seconds, followed by whole body clonic seizures

myoclonus ( J:32213 )

• many mice display seizures with facial movements, mild fore-limb clonus and mild whole body clonus lasting from 5 to 10 seconds

tonic-clonic seizures ( J:32213 )

• mice older than 6 months show severe tonic-clonic seizures lasting 30-60 seconds, with gasping and stretching all four limbs out with their tail upright, followed by severe whole body clonic seizures

abnormal microglial cell morphology ( J:32213 )

• nuclei of glial cells in corpus callosum and fimbria appear rounded rather than ellipsoid

abnormal astrocyte morphology ( J:32213 )

• astrocytes with enlarged cell bodies and thicker processes are observed in the cortex, amygdala, and hippocampus

gliosis ( J:32213 )

• present even in younger mice

astrocytosis ( J:32213 )

• present even in younger mice

abnormal neuron morphology ( J:32213 )

• neurons in the brain appear abnormal upon post-mortem; many are vacuolized, or contain clear cytoplasm around compacted and densely stained nuclei, and are usually found on the boundary of the granule layer and hilus of dentate gyrus and throughout granule layer of dentate gyrus

neuron degeneration ( J:32213 )

• degenerating neurons are present in thalamus and posterior cingulate cortex, caudate putamen, hypothalamus and CA1 and CA2 region of pyramidal layer of hippocampus

muscle

myoclonus ( J:32213 )

• many mice display seizures with facial movements, mild fore-limb clonus and mild whole body clonus lasting from 5 to 10 seconds

facial muscle spasm ( J:32213 )

respiratory system

abnormal respiration ( J:32213 )

• mice of all ages exhibit markedly increased respiratory rate in a new environment

hematopoietic system

abnormal microglial cell morphology ( J:32213 )

• nuclei of glial cells in corpus callosum and fimbria appear rounded rather than ellipsoid

immune system

abnormal microglial cell morphology ( J:32213 )

• nuclei of glial cells in corpus callosum and fimbria appear rounded rather than ellipsoid