Phenotypes associated with this allele

• Allele Symbol: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
• Allele Name: transgene insertion 6799, Robert Vassar
• Allele ID: MGI:3693208
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Qpct^tm1.2Tbay/Qpct^tm1.2Tbay Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	B6.Cg-Qpct^tm1.2Tbay Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas	MGI:4941718
cx2	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0 Tg(Prnp-MAPT*P301S)PS19Vle/0	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas Tg(Prnp-MAPT*P301S)PS19Vle	MGI:5629689
cx3	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0 Tg(Thy1-QPCT)#Tbay/0	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas Tg(Thy1-QPCT)#Tbay	MGI:4941719
cx4	Becn1^tm2.1Blev/Becn1^tm2.1Blev Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:6257020
cx5	Apoa4^tm1Bres/Apoa4^tm1Bres Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5051942
cx6	Cdk5r1^tm2.1Lht/? Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	involves: 129S4/SvJaeSor * C57BL/6 * SJL	MGI:5560900
cx7	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0 Tg(Thy1-MAPT*)30Schd/0	involves: C57BL/6 * C57BL/6J * CBA * SJL	MGI:5559229
tg8	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas	MGI:5755045
tg9	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas	MGI:5755043
tg10	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax	MGI:5604616
tg11	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * C57BL/6J * CBA * SJL	MGI:5559228
tg12	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:6257021
tg13	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * SJL	MGI:3693295
tg14	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5051941
tg15	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	involves: C57BL/6 * SJL	MGI:5560912

Genotype
MGI:4941718

cx1

• Allelic Composition: Qpct^tm1.2Tbay/Qpct^tm1.2Tbay; Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: B6.Cg-Qpct^tm1.2Tbay Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

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

nervous system

amyloid beta deposits ( J:169481 )

• at 6 months, mice exhibit a lower plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

behavior/neurological

behavior/neurological phenotype ( J:169481 )

N • spatial working memory defects observed in Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice are rescued

N • mice exhibit improved motor coordination on a beam or when suspended by a string compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

homeostasis/metabolism

amyloid beta deposits ( J:169481 )

• at 6 months, mice exhibit a lower plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

Genotype
MGI:5629689

cx2

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0; Tg(Prnp-MAPT*P301S)PS19Vle/0
• Genetic Background: B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas Tg(Prnp-MAPT*P301S)PS19Vle

homeostasis/metabolism

amyloid beta deposits ( J:211723 )

• mice develop extracellular amyloid plaque to a similar extent as mice expressing only the Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas trasngene

nervous system

amyloid beta deposits ( J:211723 )

• mice develop extracellular amyloid plaque to a similar extent as mice expressing only the Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas trasngene

abnormal hippocampus morphology ( J:211723 )

• mice show aggravation of hyperphosphorylated tau pathology that is already seen at 3 months of age

abnormal hippocampal mossy fiber morphology ( J:211723 )

• mossy fiber degeneration by 9 months of age

hippocampal neuron degeneration ( J:211723 )

loss of hippocampal neurons ( J:211723 )

• mice show reduced number of CA1 neurons at 9 months of age compared to either single mutant, indicating increased loss of hippocampal CA1 neurons

hippocampus atrophy ( J:211723 )

• hippocampal atrophy in aged mice

astrocytosis ( J:211723 )

• mice show increased astrocytosis in the cortex and thalamus at 3 months of age, and by 9 months of age, astrocytosis is strongly elevated in the hippocampus

abnormal dendrite morphology ( J:211723 )

• aged mice show a decrease in apical dendrite density in the hippocampal stratum radiatum

abnormal synapse morphology ( J:211723 )

• increase in loss of synapses

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:211723

Genotype
MGI:4941719

cx3

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0; Tg(Thy1-QPCT)#Tbay/0
• Genetic Background: B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas Tg(Thy1-QPCT)#Tbay

behavior/neurological

abnormal spatial working memory ( J:169481 )

• mice exhibit decreased alternation frequency in a Y maze compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

impaired coordination ( J:169481 )

• mice exhibit impaired motor coordination on a beam or when suspended by a string compared with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

nervous system

amyloid beta deposits ( J:169481 )

• at 6 months, mice exhibit a higher plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

homeostasis/metabolism

amyloid beta deposits ( J:169481 )

• at 6 months, mice exhibit a higher plaque load than Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas mice

Genotype
MGI:6257020

cx4

• Allelic Composition: Becn1^tm2.1Blev/Becn1^tm2.1Blev; Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

behavior/neurological

behavior/neurological phenotype ( J:244104 )

N • mice show improved performance day by day in both the escape latency and distance during the hidden platform trails of the Morris water maze compared to single Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas expressing mice

homeostasis/metabolism

amyloid beta deposits ( J:244104 )

• mice show lower levels of both soluble and insoluble amyloid beta 42 in the brain than in single Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas expressing mice

• however, expression of the precursor APP remains unaffected

• mice show a reduction of amyloid plaques in the cortex and a trend of reduction in the hippocampus

• short-term treatment of mice with SBI-0206965, an autophagy inhibitor blocking the kinase activity of an essential upstream kinase ULK1, abolishes the reduction in brain amyloid beta 42 levels

nervous system

amyloid beta deposits ( J:244104 )

• mice show lower levels of both soluble and insoluble amyloid beta 42 in the brain than in single Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas expressing mice

• however, expression of the precursor APP remains unaffected

• mice show a reduction of amyloid plaques in the cortex and a trend of reduction in the hippocampus

• short-term treatment of mice with SBI-0206965, an autophagy inhibitor blocking the kinase activity of an essential upstream kinase ULK1, abolishes the reduction in brain amyloid beta 42 levels

Genotype
MGI:5051942

cx5

• Allelic Composition: Apoa4^tm1Bres/Apoa4^tm1Bres; Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

mortality/aging

premature death ( J:169682 )

• impaired survival compared to wild-type mice and transgenic mice wild-type for Apoa4

nervous system

amyloid beta deposits ( J:169682 )

• accelerated deposition compared to transgenic mice wild-type for Apoa4

neuron degeneration ( J:169682 )

• large pyramidal neurons in cortical layer 5 and neurons in hippocampus contain more disrupted morphologies indicating enhanced neuron loss compared to transgenic mice wild-type for Apoa4

• loss of neurons is increased in areas of the cortex and CA1, CA3 of the hippocampus

behavior/neurological

abnormal spatial learning ( J:169682 )

• impaired spatial learning (slower decrease in escape latency during training in a morris water maze) compared to transgenic mice wild-type for Apoa4

abnormal long-term spatial reference memory ( J:169682 )

• more time spent in the incorrect quadrant in a probe trial in a morris water maze compared to transgenic mice wild-type for Apoa4

homeostasis/metabolism

amyloid beta deposits ( J:169682 )

• accelerated deposition compared to transgenic mice wild-type for Apoa4

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:169682

Genotype
MGI:5560900

cx6

• Allelic Composition: Cdk5r1^tm2.1Lht/?; Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6 * SJL

behavior/neurological

behavior/neurological phenotype ( J:208030 )

N • long term depression is restored to wild type levels as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

N • anxiety, cognitive performance and contextual/cued fear conditioning are restored to wild type levels as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

nervous system

nervous system phenotype ( J:208030 )

N • presence of reactive astrocytes and activated microglia is close to wild type levels as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

amyloid beta deposits ( J:208030 )

• plaque load in the hippocampus is reduced as compared to mice with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone, but still higher than wild type

• 20-30% reduction of levels of Abeta₄₂ and Abeta₄₀ in the hippocampus as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

homeostasis/metabolism

amyloid beta deposits ( J:208030 )

• plaque load in the hippocampus is reduced as compared to mice with Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone, but still higher than wild type

• 20-30% reduction of levels of Abeta₄₂ and Abeta₄₀ in the hippocampus as compared to mice carrying only Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

Genotype
MGI:5559229

cx7

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0; Tg(Thy1-MAPT*)30Schd/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA * SJL

mortality/aging

premature death ( J:201809 )

• decreased survival at 10 months of age

nervous system

amyloid beta deposits ( J:201809 )

• plaque load is reduced compared to mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

decreased brain weight ( J:201809 )

• at 9 months of age compared to wild-type mice and mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

decreased hippocampus pyramidal cell number ( J:201809 )

• at 9 months of age

neurofibrillary tangles ( J:201809 )

• detected in the hippocampus, cortex, and spinal cord

• tangles in hippocampal neurons are composed of straight filaments with a wavy appearance and of occasional paired helical filaments

• density of tangles in the spinal cord increases strongly from 3 to 9 months of age

• density of tangles in the hippocampus and cortex is increased compared to mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

• age of onset of tangles is earlier compared to mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

abnormal neurite morphology ( J:201809 )

• dilated dystrophic neurites at 9 months of age

behavior/neurological

impaired coordination ( J:201809 )

• at 6 and 8 months of age compared to wild-type mice and mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

• impairment is more severe than in mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

growth/size/body

decreased body weight ( J:201809 )

• significant and progressive reduction in body weight starting at 6 months of age

homeostasis/metabolism

amyloid beta deposits ( J:201809 )

• plaque load is reduced compared to mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:201809

Genotype
MGI:5755045

tg8

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
• Genetic Background: B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

behavior/neurological

impaired spatial learning ( J:229382 )

♀ • impaired acquisition in 2 and 5 month old females; escape latencies increase over 5 days of training

abnormal spatial reference memory ( J:229382 )

♀ • impaired spacial reference memory in 5 month old females

decreased anxiety-related response ( J:229382 )

♀ • increased open to total arm entry ratio in 2 and 5 month old females

♀ • loss of normal anxiety phenotype

limb grasping ( J:229382 )

♀ • increased clasping behavior during tail suspension in 5 month old females

impaired balance ( J:229382 )

• impairment in balance and general motor coordination in 5 month old females as measured by the balance beam

• 9 month old males either remain still on balance beam or fall off due to hind limb paresis

• poor performance in string suspension paradigm as compared to wild-type and female hemizygotes at 5 months of age

impaired coordination ( J:229382 )

• impairment in balance and general motor coordination in 5 month old females as measured by the balance beam

impaired swimming ( J:229382 )

♀ • decreased average swimming speed during cued training in 5 month old females, however no difference in day 3 escape latency

abnormal posture ( J:229382 )

♂ • postural abnormalities observed in 9 month old males

paresis ( J:229382 )

♂ • hind limb paresis in 9 month old males

pup cannibalization ( J:229382 )

♀ • in females older than 5 months of age

growth/size/body

decreased body weight ( J:229382 )

♀ • reduced body weight in 2 and 5 month old females

cachexia ( J:229382 )

♂ • wasting observed in 9 month old males

homeostasis/metabolism

amyloid beta deposits ( J:229382 )

• increased plaque load in cortex, hippocampus and thalamus at 2 (females), 5 (females) and 9 (males) months

• increase in plaque load in spinal cord of 9 month old males

• increased TBS-soluble Abeta_1-42 and Abeta_1-40 levels at 2 and 5 months (females) as compared to hemizygotes

• increased SDS-soluble Abeta_1-42 levels at 2 and 5 months (females) as compared to hemizygotes

• increased extracellular plaque load and intracellular Abeta immunoreacitivy in large spinal cord neurons in 9 month old males

nervous system

amyloid beta deposits ( J:229382 )

• increased plaque load in cortex, hippocampus and thalamus at 2 (females), 5 (females) and 9 (males) months

• increase in plaque load in spinal cord of 9 month old males

• increased TBS-soluble Abeta_1-42 and Abeta_1-40 levels at 2 and 5 months (females) as compared to hemizygotes

• increased SDS-soluble Abeta_1-42 levels at 2 and 5 months (females) as compared to hemizygotes

• increased extracellular plaque load and intracellular Abeta immunoreacitivy in large spinal cord neurons in 9 month old males

axonal spheroids ( J:229382 )

♂ • increase in axonal swellings in pons and gray matter of spinal cord of 9 month old male homozygotes as compared to hemizygotes

reproductive system

decreased litter size ( J:229382 )

♀ • in females older than 5 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:229382

Genotype
MGI:5755043

tg9

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas

behavior/neurological

decreased anxiety-related response ( J:229382 )

♀ • increased open to total arm entry ratio in 5 month old females, however, phenotype is more severe in homozygotes

limb grasping ( J:229382 )

♀ • increased clasping during tail suspension in 5 month old females as compared to controls, however clasping in homozygotes is more severe

growth/size/body

decreased body weight ( J:229382 )

♀ • reduced body weight at 2 months old females, but weight is similar to control by 5 months of age

Genotype
MGI:5604616

tg10

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax

homeostasis/metabolism

amyloid beta deposits ( J:214858 )

• retinal amyloid beta accumulates in the retinal pigment epithelial (RPE) layer and amyloid beta deposits are seen beneath the RPE layer

nervous system

amyloid beta deposits ( J:214858 )

• retinal amyloid beta accumulates in the retinal pigment epithelial (RPE) layer and amyloid beta deposits are seen beneath the RPE layer

pigmentation

abnormal retina pigment epithelium morphology ( J:214858 )

• abundant intracellular amyloid beta is seen in the cytosol of RPE and with increasing intracellular accumulation of amyloid beta, tight junction integrity is attenuated and disorganized

abnormal retina pigmentation ( J:214858 )

• 12 month old mutants show hypopigmentation in the RPE layer

vision/eye

abnormal eye morphology ( J:214858 )

• drusen-like deposit is seen between the retinal pigment epithelium (RPE) layer and Bruch membrane in 12 month old mutants

abnormal retina morphology ( J:214858 )

• large vacuoles are seen in the retina of 12 month old mutants

abnormal retina pigment epithelium morphology ( J:214858 )

• abundant intracellular amyloid beta is seen in the cytosol of RPE and with increasing intracellular accumulation of amyloid beta, tight junction integrity is attenuated and disorganized

abnormal retina pigmentation ( J:214858 )

• 12 month old mutants show hypopigmentation in the RPE layer

abnormal Bruch membrane morphology ( J:214858 )

• thickened Bruch membrane is seen in the retina of 12 month old mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:214858

Genotype
MGI:5559228

tg11

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA * SJL

mortality/aging

premature death ( J:201809 )

• decreased survival at 10 months of age

nervous system

amyloid beta deposits ( J:201809 )

homeostasis/metabolism

amyloid beta deposits ( J:201809 )

Genotype
MGI:6257021

tg12

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

behavior/neurological

abnormal spatial reference memory ( J:244104 )

• during the hidden platform trials of the Morris water maze, mice show deficiency in memorizing the platform location

• mice treated with ML246 for 5 weeks show improved performance in the Morris water maze during the hidden platform trials

• mice subjected to 16 weeks of voluntary running exercise show improved performance in the Morris water maze during the hidden platform trials

homeostasis/metabolism

amyloid beta deposits ( J:244104 )

• mice exhibit increased levels of both soluble and insoluble amyloid beta 42 in the brain

• 6 month old mice treated with ML246, a brain-penetrable autophagy-inducing small molecule, for 5 weeks show decreased levels of both soluble and insoluble amyloid beta 42 in the brain and a trend in plaque reduction, especially in the cerebral cortex

• however, expression of the precursor APP is unaffected in ML246 treated mice

• mice subjected to 16 weeks of voluntary running have lower levels of both soluble and insoluble amyloid beta 42 in brain and show a reduction of amyloid plaques than mice housed without running wheels, indicating that physical activity decreases amyloid burden

nervous system

amyloid beta deposits ( J:244104 )

• mice exhibit increased levels of both soluble and insoluble amyloid beta 42 in the brain

• 6 month old mice treated with ML246, a brain-penetrable autophagy-inducing small molecule, for 5 weeks show decreased levels of both soluble and insoluble amyloid beta 42 in the brain and a trend in plaque reduction, especially in the cerebral cortex

• however, expression of the precursor APP is unaffected in ML246 treated mice

• mice subjected to 16 weeks of voluntary running have lower levels of both soluble and insoluble amyloid beta 42 in brain and show a reduction of amyloid plaques than mice housed without running wheels, indicating that physical activity decreases amyloid burden

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:244104

Genotype
MGI:3693295

tg13

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: involves: C57BL/6 * SJL

behavior/neurological

abnormal spatial learning ( J:112949 )

• by 4-5 months of age, defects in Y-maze alternation are detected in transgenic mice, indicating impaired spatial learning/memory

nervous system

amyloid beta deposits ( J:112949 )

• mice show Abeta₄₂ deposits at 2 months of age; Abeta₄₀ levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition

• amyloid deposition increases rapidly with increasing age

• plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice

brain inflammation ( J:112949 )

• transgenic mice display neuroinflammation

abnormal hippocampus morphology ( J:112949 )

• cortical layer 1 is significantly thinner than in control brains

abnormal subiculum morphology ( J:112949 )

• neurons in subiculum are very pale, or absent

gliosis ( J:112949 )

• microgliosis and astrogliosis is seen in plaque-bearing regions of the brain by 2 months of age; numbers of activated astrocytes and microglia increases with age

astrocytosis ( J:112949 )

abnormal neuron morphology ( J:112949 )

• some neurons contain intraneuronal aggregates and display disrupted morphology

decreased cerebral cortex pyramidal cell number ( J:112949 )

• large neurons in cortical layer 5 are reduced in number

neurodegeneration ( J:112949 )

• synapse degeneration begins at 4 months of age, compared to nontransgenic controls, as shown by reduction in levels of synaptic markers; neurodeneration marker p25 level is ~150% of control at 9 and 12 months

immune system

brain inflammation ( J:112949 )

• transgenic mice display neuroinflammation

homeostasis/metabolism

amyloid beta deposits ( J:112949 )

• mice show Abeta₄₂ deposits at 2 months of age; Abeta₄₀ levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition

• amyloid deposition increases rapidly with increasing age

• plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:112949
Alzheimer's disease 3		DOID:0110042	OMIM:607822	J:112949

Genotype
MGI:5051941

tg14

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

mortality/aging

premature death ( J:169682 )

• impaired survival compared to wild-type mice

• survive longer than transgenic mice that are also Apoa4 null

nervous system

amyloid beta deposits ( J:169682 )

neuron degeneration ( J:169682 )

homeostasis/metabolism

amyloid beta deposits ( J:169682 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:169682

Genotype
MGI:5560912

tg15

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?
• Genetic Background: involves: C57BL/6 * SJL

behavior/neurological

impaired contextual conditioning behavior ( J:208030 )

• decreased % of time freezing in contextual fear conditioning test

impaired cued conditioning behavior ( J:208030 )

• decreased % of time freezing in cued fear conditioning test

abnormal response to novel object ( J:208030 )

• poor novel object recognition

hematopoietic system

increased microglial cell activation ( J:208030 )

• increased percentage of activated microglia as compared to controls

immune system

increased microglial cell activation ( J:208030 )

• increased percentage of activated microglia as compared to controls

nervous system

increased microglial cell activation ( J:208030 )

• increased percentage of activated microglia as compared to controls

amyloid beta deposits ( J:208030 )

• increased plaque load and size as compared to controls

• high levels of Abeta₄₂ and Abeta₄₀ in the hippocampus as compared to mice that also carry Cdk5r1^tm2.1Lht

abnormal astrocyte physiology ( J:208030 )

• increased percentage of reactive astrocytes as compared to controls

abnormal long-term depression ( J:208030 )

• decreased magnitude of long term depression as compared to controls

homeostasis/metabolism

amyloid beta deposits ( J:208030 )

• increased plaque load and size as compared to controls

• high levels of Abeta₄₂ and Abeta₄₀ in the hippocampus as compared to mice that also carry Cdk5r1^tm2.1Lht