Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-APPLon)2Vln
• Allele Name: transgene insertion 2, Fred Van Leuven
• Allele ID: MGI:3717572
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Psen1^tm1Vln/Psen1^tm1Vln Tg(Thy1-APPLon)2Vln/0 Tg(Thy1-cre)1Vln/0	involves: FVB/N	MGI:2684658
cx2	Tg(Hmgcr-PSEN1*M146L)#Lpr/0 Tg(Thy1-APPLon)2Vln/0	involves: C57BL/6 * CBA * FVB/N	MGI:5003462
cx3	Tg(Thy1-APPLon)2Vln/0 Tg(Thy1-BACE1)16Vln/0	involves: C57BL/6 * DBA * FVB/N	MGI:3722143
cx4	Tg(Thy1-APPLon)2Vln/0 Tg(Thy1-PSEN1*A246E)2Vln/0	involves: FVB/N	MGI:3717644
tg5	Tg(Thy1-APPLon)2Vln/0	(C57BL/6 x FVB/N)F1	MGI:3717578
tg6	Tg(Thy1-APPLon)2Vln/0	involves: C57BL/6 * CBA * FVB/N	MGI:5003461
tg7	Tg(Thy1-APPLon)2Vln/0	involves: FVB/N	MGI:3717577

Genotype
MGI:2684658

cn1

• Allelic Composition: Psen1^tm1Vln/Psen1^tm1Vln; Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-cre)1Vln/0
• Genetic Background: involves: FVB/N

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

behavior/neurological

abnormal object recognition memory ( J:87229 )

• retention of object recognition is normal at 1 hr after training but testing of animals 3 hours after familiarization with an object reveals significant impairment relative to controls

nervous system

nervous system phenotype ( J:87229 )

N • no thioflavin-S-reactive amyloid plaques or diffuse amyloid deposits are detected in mice up to 18 months of age

abnormal long-term potentiation ( J:87229 )

• with tetanic stimulation of hippocampal slices, after an initial slight decrease, the slope of the fEPSP approached control levels; LTP in transgenic brain slices is comparable to controls

Genotype
MGI:5003462

cx2

• Allelic Composition: Tg(Hmgcr-PSEN1*M146L)#Lpr/0; Tg(Thy1-APPLon)2Vln/0
• Genetic Background: involves: C57BL/6 * CBA * FVB/N

nervous system

amyloid beta deposits ( J:86694 )

• plaques are seen at 6 months of age

• as soon as detectable, a large number of deposits have a fibrillar conformation

homeostasis/metabolism

amyloid beta deposits ( J:86694 )

• plaques are seen at 6 months of age

• as soon as detectable, a large number of deposits have a fibrillar conformation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:86694

Genotype
MGI:3722143

cx3

• Allelic Composition: Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-BACE1)16Vln/0
• Genetic Background: involves: C57BL/6 * DBA * FVB/N

nervous system

amyloid beta deposits ( J:93635 )

• fibrillar thioflavin-S positive amyloid plaques are significantly increased in subiculum region of brain compared to Tg(APPV717I)1130Kha single transgenics

cerebral amyloid angiopathy ( J:93635 )

• decrease in vascular amyloid deposition is found in double transgenics relative to single mutant animals

abnormal subiculum morphology ( J:93635 )

• by 15 months, subiculum is almost totally covered with diffuse and senile plaques

abnormal cerebral cortex morphology ( J:93635 )

• at 15 months and older, surface of cerebral cortex is occupied by thioflavin-S- and amyloid beta-positive deposits is 3-5-fold greater than in age-matched Tg(APPV717I)1130Kha mice

abnormal neurite morphology ( J:93635 )

• dystrophic neurites with swollen and distorted neuritic profiles are identified in brains of mice

homeostasis/metabolism

amyloidosis ( J:93635 )

• total levels of intact amyloid beta-40 and-42 peptides are increased by ~3-fold in older mice relative to single transgenic mice

amyloid beta deposits ( J:93635 )

• fibrillar thioflavin-S positive amyloid plaques are significantly increased in subiculum region of brain compared to Tg(APPV717I)1130Kha single transgenics

cerebral amyloid angiopathy ( J:93635 )

• decrease in vascular amyloid deposition is found in double transgenics relative to single mutant animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:93635

Genotype
MGI:3717644

cx4

• Allelic Composition: Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-PSEN1*A246E)2Vln/0
• Genetic Background: involves: FVB/N

nervous system

amyloid beta deposits ( J:64209 )

• amyloid deposition occurs at 6-9 months in double mutants compared to 12-15 months in single APP transgenic mice; Abeta 42/Abeta 40 ratio is increased in young and aged mice with ratio of 3.11 at 15 months compared to 0.43 in Tg(Thy1-APP*V642I)2Vln mice at 6-9 months

• plaque-associated peptides are dramatically high in brains of double mutant mice aged 6-9 months

homeostasis/metabolism

amyloidosis ( J:64209 )

amyloid beta deposits ( J:64209 )

• amyloid deposition occurs at 6-9 months in double mutants compared to 12-15 months in single APP transgenic mice; Abeta 42/Abeta 40 ratio is increased in young and aged mice with ratio of 3.11 at 15 months compared to 0.43 in Tg(Thy1-APP*V642I)2Vln mice at 6-9 months

• plaque-associated peptides are dramatically high in brains of double mutant mice aged 6-9 months

Genotype
MGI:3717578

tg5

• Allelic Composition: Tg(Thy1-APPLon)2Vln/0
• Genetic Background: (C57BL/6 x FVB/N)F1

behavior/neurological

behavior/neurological phenotype ( J:53800 )

N • in forced swim test and a visible platform paradigm, transgenic mice perform comparably to controls indicating normal motor abilities and motivation

abnormal spatial learning ( J:53800 )

• in Morris water maze test hidden platform tests, 3-6 month old mice show significantly longer escape latencies (measure of spatial learning and memory) than non-transgenic controls

• when platform is removed, 3-6 month old mutants spend less time crossing area of the platform's former location than controls, indicating impaired cognition

Genotype
MGI:5003461

tg6

• Allelic Composition: Tg(Thy1-APPLon)2Vln/0
• Genetic Background: involves: C57BL/6 * CBA * FVB/N

nervous system

amyloid beta deposits ( J:86694 )

• plaques are seen at 13 months of age

abnormal neurite morphology ( J:86694 )

• clusters of swollen and abnormally distorted neuritic profiles are seen

homeostasis/metabolism

amyloid beta deposits ( J:86694 )

• plaques are seen at 13 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:86694

Genotype
MGI:3717577

tg7

• Allelic Composition: Tg(Thy1-APPLon)2Vln/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:53800 )

• 47.1% of animals died by 180 days of age; mortality by 360 days is 70.6% compared to 4.3% in controls

nervous system

seizures ( J:53800 )

• less than 15% of mice older than 6 months display spontaneous seizures

amyloid beta deposits ( J:53800 , J:64209 , J:93635 )

• diffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptidediffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptide (J:53800)

• mice younger than 12 months do not exhibit amyloid deposits (J:53800)

• levels of plaque peptides extracted with guanidinium hydrochloride increase exponentially in mutants >15 months of age; plaque associated peptides are not detected in brains of mice at 6-9 months of age (J:64209)

• subiculum region of brain is loaded amyloid deposits starting at 10 months of age (J:93635)

cerebral amyloid angiopathy ( J:93635 )

• amyloid deposits are found in the parenchyma and in cortical and leptimenigeal arterioles in brains at 16 months

abnormal subiculum morphology ( J:93635 )

• by 15 months, subiculum is almost totally covered with diffuse and senile plaques

abnormal neurite morphology ( J:93635 )

• dystrophic neurites with swollen and distorted neuritic profiles are identified in brains of mice

reduced long-term potentiation ( J:53800 , J:87229 )

• tetanic stimulation in hippocampal brain slices triggers significantly impaired LTP; LTP progressively decreases in brain slices (J:87229)

behavior/neurological

abnormal response to new environment ( J:53800 )

• ambulation measured in a corner-crossing variant upon transfer to a new cage is reduced relative to controls at 4-9 weeks of age, 12-17, and 20-52 weeks with differences becoming more pronounced with age

hyperactivity ( J:53800 )

• mice exhibit increased episodes of agitation and spontaneous activity by 8 weeks of age onward

seizures ( J:53800 )

• less than 15% of mice older than 6 months display spontaneous seizures

homeostasis/metabolism

amyloidosis ( J:64209 , J:87229 )

• in brains of 10-12 month-old mice, diffuse and senile amyloid plaques are present and increase exponentially with age (J:87229)

amyloid beta deposits ( J:53800 , J:64209 , J:93635 )

• diffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptidediffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptide (J:53800)

• mice younger than 12 months do not exhibit amyloid deposits (J:53800)

• levels of plaque peptides extracted with guanidinium hydrochloride increase exponentially in mutants >15 months of age; plaque associated peptides are not detected in brains of mice at 6-9 months of age (J:64209)

• subiculum region of brain is loaded amyloid deposits starting at 10 months of age (J:93635)

cerebral amyloid angiopathy ( J:93635 )

• amyloid deposits are found in the parenchyma and in cortical and leptimenigeal arterioles in brains at 16 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:93635