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: 17 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
cx8	Ms4a4a^em1Cmk/Ms4a4a^em1Cmk Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:8257821
tg9	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax	MGI:5755045
tg10	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas	MGI:5755043
tg11	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax	MGI:5604616
tg12	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * C57BL/6J * CBA * SJL	MGI:5559228
tg13	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:6257021
tg14	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0	involves: C57BL/6 * SJL	MGI:3693295
tg15	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax	MGI:8161062
tg16	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5051941
tg17	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

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

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

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

cellular

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

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:8257821

cx8

• Allelic Composition: Ms4a4a^em1Cmk/Ms4a4a^em1Cmk; Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

nervous system

abnormal microglial cell physiology ( J:371923 )

• microglia from whole brains of 6-month-old mice exhibit a shift towards a pro-inflammatory state, as shown by a significant increase in the frequencies of CD45-mid/CD11b-positive microglia expressing CD86 (a pro-inflammatory marker) and Cxcr4^hi (a chemokine receptor involved in inflammation)

• moreover, microglia produce more matrix metalloproteinase 9 (MMP-9), a microglia-enriched Abeta-degrading enzyme that can digest both soluble and fibrillar forms of amyloid beta (Abeta)

• however, microglial recruitment to plaques is normal and the overall levels of microgliosis and astrogliosis remain unaffected in the aged hippocampus and cortex

amyloid beta deposits ( J:371923 )

• at 6 months of age, brains show a significantly lower amyloid beta (Abeta) plaque burden, as defined by the area of HJ3.4 coverage, in the hippocampus and cortex than in control mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

• average plaque size is significantly decreased in the aged hippocampus while the number of plaques per 1000 um² within the hippocampus is relatively normal

• aged mice have significantly fewer smaller plaques in the hippocampus (602-1301 um²) and cortex (600-1649 um²) than control mice

• brain sections co-stained with X-34 (beta-sheet-rich, dense core) and HJ3.4 (total Abeta) indicates significantly more compact plaques in the aged hippocampus

• in aged brains, full-length APP protein levels are relatively normal but C-terminal fragment alpha (CTF-alpha, C83) levels are significantly decreased while CTF-beta (C99) levels are reduced to a lesser extent, suggesting more efficient APP processing and/or degradation

• however, X-34-positive plaques in the cortex are similar to those in control mice and no differences in neuritic dystrophy are detected near plaques in the aged hippocampus or cortex

increased brain enzyme/coenzyme level ( J:371923 )

• brain homogenates from 6-month-old mice show significantly increased protein levels of MMP-9 in the RAB-soluble fraction (enriched for secreted proteins) with no major changes detected in IDE, NEP or cathepsin B protein levels in this fraction

• MMP-9 protein levels are also significantly increased in RAB-soluble protein fraction of 6-week-old mice, prior to plaque accumulation

• cathepsin B levels are significantly reduced in the RIPA-soluble fraction which contains membrane-bound proteins, with no major changes detected in MMP-9, IDE, and NEP levels in this fraction

homeostasis/metabolism

amyloid beta deposits ( J:371923 )

• at 6 months of age, brains show a significantly lower amyloid beta (Abeta) plaque burden, as defined by the area of HJ3.4 coverage, in the hippocampus and cortex than in control mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

• average plaque size is significantly decreased in the aged hippocampus while the number of plaques per 1000 um² within the hippocampus is relatively normal

• aged mice have significantly fewer smaller plaques in the hippocampus (602-1301 um²) and cortex (600-1649 um²) than control mice

• brain sections co-stained with X-34 (beta-sheet-rich, dense core) and HJ3.4 (total Abeta) indicates significantly more compact plaques in the aged hippocampus

• in aged brains, full-length APP protein levels are relatively normal but C-terminal fragment alpha (CTF-alpha, C83) levels are significantly decreased while CTF-beta (C99) levels are reduced to a lesser extent, suggesting more efficient APP processing and/or degradation

• however, X-34-positive plaques in the cortex are similar to those in control mice and no differences in neuritic dystrophy are detected near plaques in the aged hippocampus or cortex

decreased amyloid deposition ( J:371923 )

• in vivo microdialysis of 8-week-old mice shows that baseline levels of soluble amyloid beta (Abeta) in the brain (hippocampal) interstitial fluid (ISF) are significantly lower than in control mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

• after i.p. treatment with a gamma-secretase inhibitor to prevent new Abeta production, the elimination rate of soluble Abeta in brain ISF is significantly faster than in control mice, indicating that Abeta half-life is reduced prior to plaque accumulation

• however, decreased ISF Abeta levels are not due to altered amyloid precursor protein (APP) processing, as both expression of APP processing genes and protein levels of full-length APP and its C-terminal fragments are normal in 6-week-old brains

increased brain enzyme/coenzyme level ( J:371923 )

• brain homogenates from 6-month-old mice show significantly increased protein levels of MMP-9 in the RAB-soluble fraction (enriched for secreted proteins) with no major changes detected in IDE, NEP or cathepsin B protein levels in this fraction

• MMP-9 protein levels are also significantly increased in RAB-soluble protein fraction of 6-week-old mice, prior to plaque accumulation

• cathepsin B levels are significantly reduced in the RIPA-soluble fraction which contains membrane-bound proteins, with no major changes detected in MMP-9, IDE, and NEP levels in this fraction

immune system

abnormal microglial cell physiology ( J:371923 )

• microglia from whole brains of 6-month-old mice exhibit a shift towards a pro-inflammatory state, as shown by a significant increase in the frequencies of CD45-mid/CD11b-positive microglia expressing CD86 (a pro-inflammatory marker) and Cxcr4^hi (a chemokine receptor involved in inflammation)

• moreover, microglia produce more matrix metalloproteinase 9 (MMP-9), a microglia-enriched Abeta-degrading enzyme that can digest both soluble and fibrillar forms of amyloid beta (Abeta)

• however, microglial recruitment to plaques is normal and the overall levels of microgliosis and astrogliosis remain unaffected in the aged hippocampus and cortex

hematopoietic system

abnormal microglial cell physiology ( J:371923 )

• microglia from whole brains of 6-month-old mice exhibit a shift towards a pro-inflammatory state, as shown by a significant increase in the frequencies of CD45-mid/CD11b-positive microglia expressing CD86 (a pro-inflammatory marker) and Cxcr4^hi (a chemokine receptor involved in inflammation)

• moreover, microglia produce more matrix metalloproteinase 9 (MMP-9), a microglia-enriched Abeta-degrading enzyme that can digest both soluble and fibrillar forms of amyloid beta (Abeta)

• however, microglial recruitment to plaques is normal and the overall levels of microgliosis and astrogliosis remain unaffected in the aged hippocampus and cortex

cellular

abnormal microglial cell physiology ( J:371923 )

• microglia from whole brains of 6-month-old mice exhibit a shift towards a pro-inflammatory state, as shown by a significant increase in the frequencies of CD45-mid/CD11b-positive microglia expressing CD86 (a pro-inflammatory marker) and Cxcr4^hi (a chemokine receptor involved in inflammation)

• moreover, microglia produce more matrix metalloproteinase 9 (MMP-9), a microglia-enriched Abeta-degrading enzyme that can digest both soluble and fibrillar forms of amyloid beta (Abeta)

• however, microglial recruitment to plaques is normal and the overall levels of microgliosis and astrogliosis remain unaffected in the aged hippocampus and cortex

Genotype
MGI:5755045

tg9

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

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

tg10

• 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

tg11

• 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

tg12

• 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

tg13

• 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

tg14

• 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

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 )

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

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

cellular

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 )

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:8161062

tg15

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

behavior/neurological

impaired spatial working memory ( J:360724 )

• mice exhibit reduced spontaneous alternation in the Y-maze

• mice administered an anti-FAM19A5 antibody intravenously at 8 months of age show increased spontaneous alternation and thus improved performance in the Y-maze test

abnormal response to novel object ( J:360724 )

• mice do not exhibit a preference for the novel object in the novel object recognition test

• mice treated with an anti-FAM195A antibody at 8 months of age show enhanced exploration of a novel object in the novel object recognition test

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:360724

Genotype
MGI:5051941

tg16

• 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

tg17

• 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

abnormal astrocyte physiology ( J:208030 )

• increased percentage of reactive astrocytes as compared to controls

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 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

cellular

abnormal astrocyte physiology ( J:208030 )

• increased percentage of reactive astrocytes as compared to controls

increased microglial cell activation ( J:208030 )

• increased percentage of activated microglia as compared to controls