Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-APP)3Somm
• Allele Name: transgene insertion 3, Bernd Sommer
• Allele ID: MGI:2447146
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Prnp-ITM2B*)6Jckr/0 Tg(Thy1-APP)3Somm/0	B6.Cg-Tg(Prnp-ITM2B*)6Jckr Tg(Thy1-APP)3Somm	MGI:4452490
cx2	Lamp5^em1Lmit/Lamp5^em1Lmit Tg(Thy1-APP)3Somm/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:7608060
cx3	Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx Tg(Thy1-APP)3Somm/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:4833965
cx4	Lamp5^em1Lmit/Lamp5^+ Tg(Thy1-APP)3Somm/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:7608059
cx5	Abca1^tm1Jdm/Abca1^tm1Jdm Tg(Thy1-APP)3Somm/0	involves: C57BL/6J * DBA/1LacJ * DBA/2	MGI:4833954
tg6	Tg(Thy1-APP)3Somm/0	B6.Cg-Tg(Thy1-APP)3Somm	MGI:3720731
tg7	Tg(Thy1-APP)3Somm/0	involves: C57BL/6 * C57BL/6J * DBA/2	MGI:7608058
tg8	Tg(Thy1-APP)3Somm/0	involves: C57BL/6J * DBA/2	MGI:2652447

Genotype
MGI:4452490

cx1

• Allelic Composition: Tg(Prnp-ITM2B*)6Jckr/0; Tg(Thy1-APP)3Somm/0
• Genetic Background: B6.Cg-Tg(Prnp-ITM2B*)6Jckr Tg(Thy1-APP)3Somm

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

nervous system

amyloid beta deposits ( J:159279 )

• at 13 months, mice exhibit a 70% reduction in neocortical amyloid beta deposition compared with Tg(Thy1-APP)3Somm mice

homeostasis/metabolism

amyloidosis ( J:159279 )

• mice exhibit an accumulation of Dan-amyloid in separate plaques from amyloid beta plaques

amyloid beta deposits ( J:159279 )

• at 13 months, mice exhibit a 70% reduction in neocortical amyloid beta deposition compared with Tg(Thy1-APP)3Somm mice

Genotype
MGI:7608060

cx2

• Allelic Composition: Lamp5^em1Lmit/Lamp5^em1Lmit; Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

premature death ( J:345459 )

• mice exhibit earlier and more rapid mortality and poor overall survival compared to single Tg(Thy1-APP)3Somm hemizygotes

behavior/neurological

hyperactivity ( J:345459 )

• mice show increased hyperactivity over the entire test period compared to single Tg(Thy1-APP)3Somm hemizygotes

• memory could not be tested due to high premature mortality rate

nervous system

abnormal brain wave pattern ( J:345459 )

• hippocampal EEG recordings show a further increase in spontaneous discharges and spike trains than seen in single Tg(Thy1-APP)3Somm hemizygotes

• spectral power at gamma (30-100 Hz) frequency is increased more than in single Tg(Thy1-APP)3Somm hemizygotes or Lamp5^em1Lmit/Lamp5⁺ Tg(Thy1-APP)3Somm/0 mice, indicating neuronal network hypersynchronicity

• theta/gamma cross frequency coupling, an EEG measure linked to memory, is disrupted more than in single Tg(Thy1-APP)3Somm hemizygotes

Genotype
MGI:4833965

cx3

• Allelic Composition: Tnfrsf1a^tm1Imx/Tnfrsf1a^tm1Imx; Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

nervous system

nervous system phenotype ( J:134832 )

N • at 24 months, mice exhibit little neuronal loss unlike Tg(Thy1-APP)3Somm mice

microgliosis ( J:134832 )

• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

amyloid beta deposits ( J:134832 )

• at 24 months, mice exhibit reduced amyloid plaques compared with Tg(Thy1-APP)3Somm mice

cerebral amyloid angiopathy ( J:134832 )

• mice exhibit reduced cerebral amyloid angiopathy compared with Tg(Thy1-APP)3Somm mice

behavior/neurological

behavior/neurological phenotype ( J:134832 )

N • mice exhibit normal exploratory learning and memory retention unlike Tg(Thy1-APP)3Somm mice

hematopoietic system

microgliosis ( J:134832 )

• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

immune system

microgliosis ( J:134832 )

• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

homeostasis/metabolism

amyloid beta deposits ( J:134832 )

• at 24 months, mice exhibit reduced amyloid plaques compared with Tg(Thy1-APP)3Somm mice

cerebral amyloid angiopathy ( J:134832 )

• mice exhibit reduced cerebral amyloid angiopathy compared with Tg(Thy1-APP)3Somm mice

Genotype
MGI:7608059

cx4

• Allelic Composition: Lamp5^em1Lmit/Lamp5⁺; Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

premature death ( J:345459 )

• survival is reduced similarly to that seen in single Tg(Thy1-APP)3Somm hemizygotes until 150 days and thereafter shows a trend towards increased mortality

behavior/neurological

impaired spatial learning ( J:345459 )

• learning in the Morris water maze is impaired compared to single Tg(Thy1-APP)3Somm hemizygotes at 12 months of age

abnormal spatial reference memory ( J:345459 )

• memory formation in the Morris water maze is impaired compared to single Tg(Thy1-APP)3Somm hemizygotes at 12 months of age

homeostasis/metabolism

amyloid beta deposits ( J:345459 )

• amyloid beta formation and plaque load in aged mice is similar to single Tg(Thy1-APP)3Somm hemizygotes

nervous system

amyloid beta deposits ( J:345459 )

• amyloid beta formation and plaque load in aged mice is similar to single Tg(Thy1-APP)3Somm hemizygotes

abnormal brain wave pattern ( J:345459 )

• spectral power at gamma (30-100 Hz) frequency is increased more than in single Tg(Thy1-APP)3Somm hemizygotes, indicating neuronal network hypersynchronicity

• theta/gamma cross frequency coupling, an EEG measure linked to memory, is disrupted more than in single Tg(Thy1-APP)3Somm hemizygotes

Genotype
MGI:4833954

cx5

• Allelic Composition: Abca1^tm1Jdm/Abca1^tm1Jdm; Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6J * DBA/1LacJ * DBA/2

mortality/aging

preweaning lethality, incomplete penetrance ( J:105902 )

• fewer than expected mice are present at weaning

nervous system

intracerebral hemorrhage ( J:105902 )

• mice exhibit more cerebral amyloid angiopathy-associated cerebral hemorrhage than Tg(Thy1-APP)3Somm mice

cerebral amyloid angiopathy ( J:105902 )

• at 13 months, mice exhibit more cerebral amyloid angiopathy than in Tg(Thy1-APP)3Somm mice

cardiovascular system

intracerebral hemorrhage ( J:105902 )

• mice exhibit more cerebral amyloid angiopathy-associated cerebral hemorrhage than Tg(Thy1-APP)3Somm mice

homeostasis/metabolism

amyloidosis ( J:105902 )

• mice exhibit a 2-fold increase in insoluble beta-amyloid in the brain compared with Tg(Thy1-APP)3Somm mice

cerebral amyloid angiopathy ( J:105902 )

• at 13 months, mice exhibit more cerebral amyloid angiopathy than in Tg(Thy1-APP)3Somm mice

Genotype
MGI:3720731

tg6

• Allelic Composition: Tg(Thy1-APP)3Somm/0
• Genetic Background: B6.Cg-Tg(Thy1-APP)3Somm

nervous system

amyloid beta deposits ( J:80919 )

• amyloid plaques are associated with alterations in axonal growth and ectopic synaptic differentiation

cerebral amyloid angiopathy ( J:80919 )

• vascular amyloid is associated with ectopic entorhinal boutons

abnormal axon morphology ( J:80919 )

• axons that line the periphery of beta-amyloid plaques exhibit swelling unlike in wild-type mice

• entorhinal fibers extend outside the termination zone unlike in wild-type mice

• commissure axons extend into the outer molecular layer unlike in wild-type mice

• amyloid plaques are associated with alterations in axonal growth and ectopic synaptic differentiation

• vascular amyloid is associated with ectopic entorhinal boutons

behavior/neurological

increased exploration in new environment ( J:101283 )

• at 6 months during the first 2 hours

abnormal spatial learning ( J:80449 )

• impaired acquisition in the Morris water maze; the number of quadrant entries and the escape latencies are higher than in controls

• however, mutants are unaffected in open-field, elevated plus-maze, emergence tests, tests measuring motor coordination, during the probe trial and while swimming towards a visible platform

increased aggression towards mice ( J:152518 )

• in an isolation-induced/resident-intruder paradigm, mice exhibit a 4.6- and 59-fold increase in aggression at 6 and 12 months, respectively, compared with wild-type mice

jumpy ( J:80449 )

• 67% of animals exhibit myoclonic jumping behavior in home cage

abnormal locomotor activation ( J:80449 )

• reduced number of horizontal and vertical movements in the photocell monitor

abnormal locomotor circadian rhythm ( J:101283 )

• at 3 months, mice exhibit lower light ambulation compared with wild-type mice

• at 6 months, mice exhibit increased in the ratio of dark to light ambulation during the second half of the active phase compared with wild-type mice

• at 12 months, circadian locomotor patterns are more constant than in wild-type mice

• at 12 months, mice exhibit increased dark and total ambulation compared with wild-type mice

• at 12 months, dark ambulation level is bimodal unlike in wild-type mice

hyperactivity ( J:101283 )

• overnight at 12 months

growth/size/body

decreased body weight ( J:80449 )

• 29% weight reduction compared to wild-type

homeostasis/metabolism

amyloid beta deposits ( J:80919 )

• amyloid plaques are associated with alterations in axonal growth and ectopic synaptic differentiation

cerebral amyloid angiopathy ( J:80919 )

• vascular amyloid is associated with ectopic entorhinal boutons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:80449

Genotype
MGI:7608058

tg7

• Allelic Composition: Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA/2

mortality/aging

premature death ( J:345459 )

• male, and more so, female mice show reduced survival

behavior/neurological

abnormal habituation to a new environment ( J:345459 )

• 2-month-old mice present with slower habituation in the open field test, before development of memory deficits

hyperactivity ( J:345459 )

• 2-month-old mice present with in the open field test, before development of memory deficits

homeostasis/metabolism

amyloid beta deposits ( J:345459 )

• amyloid beta formation and plaque

nervous system

amyloid beta deposits ( J:345459 )

• amyloid beta formation and plaque

abnormal brain wave pattern ( J:345459 )

• hippocampal EEG recordings show increased spontaneous discharges and spike trains compared to controls

• spectral power analysis shows increased high frequency power compared to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:345459

Genotype
MGI:2652447

tg8

• Allelic Composition: Tg(Thy1-APP)3Somm/0
• Genetic Background: involves: C57BL/6J * DBA/2

nervous system

abnormal brain vasculature morphology ( J:67583 )

• mice exhibit aneurysm-like vasodilation unlike in wild-type mice

intracerebral hemorrhage ( J:67583 )

• mice exhibit blood vessel ruptures that range from microhemorrhages to large hematomas unlike wild-type mice

impaired blood-brain barrier function ( J:67583 )

• mice exhibit leakage in the blood-brain barrier unlike wild-type mice

microgliosis ( J:134832 )

amyloid beta deposits ( J:44603 , J:134832 )

• develop amyloid beta deposits in the neocortex and hippocampus starting at 6 months of age, which increase in size and number with age (J:44603)

• by 24 months of age, deposits occupy a substantial area of the neocortex and hippocampus and are found in the thalamus and olfactory nucleus and are isolated in the caudate putamen (J:44603)

• develop almost exclusively congophilic plaques already at their first appearance (J:44603)

• at 24 months (J:134832)

cerebral amyloid angiopathy ( J:67583 , J:134832 )

• in the neocortex, hippocampus, and thalamus and to a lesser degree in other regions such as septum, striatum, brainstem, and white matter (J:67583)

brain inflammation ( J:44603 )

• mutants exhibit inflammatory responses in the brain, showing a massive glial response

abnormal hippocampus pyramidal cell morphology ( J:44603 )

• loss of pyramidal neurons in the vicinity of amyloid beta deposits in the CA3 area

abnormal cholinergic neuron morphology ( J:44603 )

• local distortion of the cholinergic fiber network is seen in the vicinity of plaques

decreased neuron number ( J:44603 )

• local loss of neurons in the vicinity of plaques

neuron degeneration ( J:134832 )

• at 24 months

immune system

microgliosis ( J:134832 )

brain inflammation ( J:44603 )

• mutants exhibit inflammatory responses in the brain, showing a massive glial response

cardiovascular system

abnormal brain vasculature morphology ( J:67583 )

• mice exhibit aneurysm-like vasodilation unlike in wild-type mice

vascular smooth muscle hypoplasia ( J:67583 )

• mice exhibit smooth muscle cell degeneration in amyloid laden blood vessels unlike wild-type mice

abnormal blood circulation ( J:129162 )

• bicuculline-treated mice exhibit delayed and reduced amplitude of changes in cerebral blood volume compared with similarly treated wild-type mice

• at 25 months, acetazolamide-treated mice exhibit a smaller increase in the percent change of cerebral blood volume compared with similarly treated wild-type mice

intracerebral hemorrhage ( J:67583 )

• mice exhibit blood vessel ruptures that range from microhemorrhages to large hematomas unlike wild-type mice

impaired blood-brain barrier function ( J:67583 )

• mice exhibit leakage in the blood-brain barrier unlike wild-type mice

vascular inflammation ( J:67583 )

• mice exhibit cerebral amyloid angiopathy associated vasculitis unlike wild-type mice

muscle

vascular smooth muscle hypoplasia ( J:67583 )

• mice exhibit smooth muscle cell degeneration in amyloid laden blood vessels unlike wild-type mice

homeostasis/metabolism

amyloid beta deposits ( J:44603 , J:134832 )

• develop amyloid beta deposits in the neocortex and hippocampus starting at 6 months of age, which increase in size and number with age (J:44603)

• by 24 months of age, deposits occupy a substantial area of the neocortex and hippocampus and are found in the thalamus and olfactory nucleus and are isolated in the caudate putamen (J:44603)

• develop almost exclusively congophilic plaques already at their first appearance (J:44603)

• at 24 months (J:134832)

cerebral amyloid angiopathy ( J:67583 , J:134832 )

• in the neocortex, hippocampus, and thalamus and to a lesser degree in other regions such as septum, striatum, brainstem, and white matter (J:67583)

decreased physiological sensitivity to xenobiotic ( J:129162 )

• bicuculline-treated mice exhibit delayed and reduced amplitude of changes in cerebral blood volume compared with similarly treated wild-type mice

• at 25 months, acetazolamide-treated mice exhibit a smaller increase in the percent change of cerebral blood volume compared with similarly treated wild-type mice

abnormal response to injury ( J:134661 )

• during posthypoxic recovery, the spike amplitude in hippocampal region CA1 after stimulation of Schaffer collaterals in region CA3 is less than in similarly treated wild-type mice

• at 4 months, hypoxic tolerance is impaired compared to in similarly treated wild-type mice

behavior/neurological

abnormal learning/memory/conditioning ( J:134832 )

• at 6 months, mice exhibit reduced exploratory learning compared with wild-type mice

abnormal object recognition memory ( J:134832 )

• object recognition is impaired compared to in wild-type mice

hematopoietic system

microgliosis ( J:134832 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:44603
cerebral amyloid angiopathy		DOID:9246		J:67583