Phenotypes associated with this allele

• Allele Symbol: Tg(PRNP-APPSweInd)8Dwst
• Allele Name: transgene insertion 8, David Westaway
• Allele ID: MGI:3589475
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Azdm1^A/J/Azdm1^A/J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818007
cx2	Azdm2^A/J/Azdm2^A/J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818010
cx3	Azdm3^A/J/Azdm3^C57BL/6J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818011
cx4	Azdm3^A/J/Azdm3^A/J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818012
cx5	Azdm4^A/J/Azdm4^C57BL/6J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818013
cx6	Azdm4^A/J/Azdm4^A/J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818014
cx7	Azdm1^A/J/Azdm1^C57BL/6J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818008
cx8	Azdm2^A/J/Azdm2^C57BL/6J Tg(PRNP-APPSweInd)8Dwst/0	involves: A/J * C57BL/6J	MGI:3818009
cx9	Npc1^m1N/Npc1^m1N Tg(PRNP-APPSweInd)8Dwst/0	involves: BALB/c * C3H/HeJ * C57BL/6J	MGI:5442379
cx10	Atp7b^tx-J/Atp7b^tx-J Tg(PRNP-APPSweInd)8Dwst/0	involves: C3H/HeJ * C57BL/6	MGI:3793275
cx11	Tg(PRNP-APPSweInd)8Dwst/0 Tg(PSEN1)1098Citr/0	involves: C3H/HeJ * C57BL/6J * FVB/N	MGI:3722166
cx12	Tg(Camk2a-ITM2B)8.4Ldad/0 Tg(PRNP-APPSweInd)8Dwst/0	involves: C3H/HeJ * C57BL/6J * FVB/N	MGI:3810992
cx13	Tg(PRNP-APPSweInd)8Dwst/0 Tg(PSEN1*L286V)1274Citr/0	involves: C3H/HeJ * C57BL/6J * FVB/N	MGI:3722165
tg14	Tg(PRNP-APPSweInd)8Dwst/0	involves: 129S6/SvEvTac * C3H/HeJ * C57BL/6J	MGI:3722163
tg15	Tg(PRNP-APPSweInd)8Dwst/0	involves: C3H/HeJ * C57BL/6	MGI:3793276
tg16	Tg(PRNP-APPSweInd)8Dwst/0	involves: C3H/HeJ * C57BL/6J	MGI:3722160
tg17	Tg(PRNP-APPSweInd)8Dwst/0	involves: C3H/HeJ * C57BL/6J * FVB/N	MGI:3722161
tg18	Tg(PRNP-APPSweInd)8Dwst/?	involves: 129S6/SvEvTac	MGI:3665287

Genotype
MGI:3818007

cx1

• Allelic Composition: Azdm1^A/J/Azdm1^A/J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

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

nervous system

amyloid beta deposits ( J:112037 )

• decreased brain amyloid-beta 40 and 42

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid burden

• decreased brain amyloid plaque number

amyloid beta deposits ( J:112037 )

• decreased brain amyloid-beta 40 and 42

Genotype
MGI:3818010

cx2

• Allelic Composition: Azdm2^A/J/Azdm2^A/J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid burden

• decreased brain amyloid plaque number

Genotype
MGI:3818011

cx3

• Allelic Composition: Azdm3^A/J/Azdm3^C57BL/6J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid burden

• decreased brain amyloid plaque number

Genotype
MGI:3818012

cx4

• Allelic Composition: Azdm3^A/J/Azdm3^A/J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid burden

• decreased brain amyloid plaque number

Genotype
MGI:3818013

cx5

• Allelic Composition: Azdm4^A/J/Azdm4^C57BL/6J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid plaque number

Genotype
MGI:3818014

cx6

• Allelic Composition: Azdm4^A/J/Azdm4^A/J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid plaque number

Genotype
MGI:3818008

cx7

• Allelic Composition: Azdm1^A/J/Azdm1^C57BL/6J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

nervous system

amyloid beta deposits ( J:112037 )

• decreased brain amyloid-beta 40 and 42

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid burden

• decreased brain amyloid plaque number

amyloid beta deposits ( J:112037 )

• decreased brain amyloid-beta 40 and 42

Genotype
MGI:3818009

cx8

• Allelic Composition: Azdm2^A/J/Azdm2^C57BL/6J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: A/J * C57BL/6J

homeostasis/metabolism

amyloidosis ( J:112037 )

• decreased brain amyloid burden

• decreased brain amyloid plaque number

Genotype
MGI:5442379

cx9

• Allelic Composition: Npc1^m1N/Npc1^m1N; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: BALB/c * C3H/HeJ * C57BL/6J

mortality/aging

premature death ( J:188345 )

• mutants have a maximum lifespan of 77 days, with mortality rate increasing drastically from 55 days onward

• mutants treated with 2-hydroxypropyl-beta-cyclodextrin (2-HPC) at P7 to lower cholesterol accumulation live significantly longer than saline-injected mutants, with a median survival of 103 days versus 69 days

growth/size/body

decreased body weight ( J:188345 )

• mutants reach a maximum body weight of approximately 12 grams by 6 weeks of age which is about 30% less compared to controls

weight loss ( J:188345 )

• weight declines progressively after 6 weeks of age until death

behavior/neurological

abnormal object recognition memory ( J:188345 )

• mutants exhibit deficits in object memory index at 7 and 10 weeks of age; object recognition memory deficits are accelerated compared to single Npc1 homozygotes

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in cognitive performance

impaired coordination ( J:188345 )

• mutants exhibit impaired rotarod performance and gait coordination at 7 weeks of age which is further exacerbated by 10 weeks of age

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance

decreased locomotor activity ( J:188345 )

• mutants exhibit reduced locomotor activity and increased periods of inactivity in open-field tests at both 7 and 10 weeks of age

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance

nervous system

microgliosis ( J:188345 )

• mutants exhibit microglial activation in the hippocampus and cerebellum at a higher level than in single Npc1 homozygotes

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants

increased brain cholesterol level ( J:188345 )

• mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age

• however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls

astrocytosis ( J:188345 )

• mutants exhibit a profound increase in the number and activation of glial fibrillary acidic protein (GFAP)-labeled astrocytes in the hippocampus and cerebellum compared with wild-type, single Tg(PRNP-APPSweInd)8Dwst mutants, and single Npc1 homozygotes

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show decreased astrocyte activation compared to saline-injected mutants

neurodegeneration ( J:188345 )

• neurodgeneration in the cerebellum is accelerated compared to single Npc1 homozygotes

Purkinje cell degeneration ( J:188345 )

• decrease in the number of cerebellar Purkinje cells that is more pronounced than in single Npc1 homozygotes

• however neuronal loss in the hippocampus is not seen

demyelination ( J:188345 )

• mutants exhibit a loss of myelin fibre tracts in the hippocampus/cortex and cerebellum, indicating significant demyelination; demyelination is more severe than in single Npc1 homozygotes

hematopoietic system

microgliosis ( J:188345 )

• mutants exhibit microglial activation in the hippocampus and cerebellum at a higher level than in single Npc1 homozygotes

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:188345 )

• cathepsin D levels are higher in the hippocampus and the cerebellum than in controls, including single Npc1 homozygotes

• cytosolic cathepsin D, cytochrome c and Bcl-2-associated X protein levels are increased in the cerebellum to a higher level than in single Npc1 homozygotes

increased brain cholesterol level ( J:188345 )

• mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age

• however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls

abnormal enzyme/coenzyme activity ( J:188345 )

• cathepsin D activity is higher in the hippocampus and the cerebellum than in controls, including single Npc1 homozygotes

immune system

microgliosis ( J:188345 )

• mutants exhibit microglial activation in the hippocampus and cerebellum at a higher level than in single Npc1 homozygotes

• mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:188345
Niemann-Pick disease		DOID:14504		J:188345

Genotype
MGI:3793275

cx10

• Allelic Composition: Atp7b^tx-J/Atp7b^tx-J; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: C3H/HeJ * C57BL/6

mortality/aging

mortality/aging ( J:86701 )

N • survival is increased compared to in Tg(PRNP-APPSweInd)8Dwst mice

homeostasis/metabolism

amyloid beta deposits ( J:86701 )

• mice exhibit a 45% reduction in plaque area compared to in Tg(PRNP-APPSweInd)8Dwst mice due to a reduction in the number of plaques

increased copper level ( J:86701 )

• copper levels are increased compared to in heterozygous Atp7b^tx-J mice

nervous system

amyloid beta deposits ( J:86701 )

• mice exhibit a 45% reduction in plaque area compared to in Tg(PRNP-APPSweInd)8Dwst mice due to a reduction in the number of plaques

Genotype
MGI:3722166

cx11

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/0; Tg(PSEN1)1098Citr/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J * FVB/N

homeostasis/metabolism

amyloidosis ( J:69967 )

• amyloid deposition is enhanced when the PSEN1 transgene is also expressed by mutants; deposition is noted by 30-45 days of age

Genotype
MGI:3810992

cx12

• Allelic Composition: Tg(Camk2a-ITM2B)8.4Ldad/0; Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J * FVB/N

nervous system

amyloid beta deposits ( J:138796 )

• reduction in plaque formation compared to mice carrying just Tg(PRNP-APPSweInd)8Dwst

homeostasis/metabolism

amyloid beta deposits ( J:138796 )

• reduction in plaque formation compared to mice carrying just Tg(PRNP-APPSweInd)8Dwst

Genotype
MGI:3722165

cx13

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/0; Tg(PSEN1*L286V)1274Citr/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J * FVB/N

homeostasis/metabolism

amyloidosis ( J:69967 )

• amyloid deposition is enhanced when the PSEN1 transgene is also expressed by mutants; deposition is noted by 30-45 days of age

Genotype
MGI:3722163

tg14

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: 129S6/SvEvTac * C3H/HeJ * C57BL/6J

mortality/aging

premature death ( J:69967 )

• Background Sensitivity: survival decreases to 25-40% within 120 days of life; only 17% (7/41) survive to 365 days

Genotype
MGI:3793276

tg15

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: C3H/HeJ * C57BL/6

homeostasis/metabolism

abnormal copper level ( J:86701 )

• copper levels are decreased compared to in non-transgenic mice

Genotype
MGI:3722160

tg16

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J

Increase in creatine deposits in hippocampus of Tg(PRNP-APPSweInd)8Dwst/0 mice with age

mortality/aging

premature death ( J:69967 )

• Background Sensitivity: 20/52 mice die before 120 days, 3/52 by 130 days and 3/52 die after 250 days; 50% survive for at least a year

behavior/neurological

abnormal spatial learning ( J:69967 )

• mice show impairment in acquisition of spatial information during place discrimination training at 11 weeks of age; mice show longer latencies to reach escape platform and longer search paths to reach platform

abnormal spatial reference memory ( J:69967 )

• during probe trial after completion of training, mice display lower annulus crossing index, searching for platform in a circular fashion and often crossing the centers of alternative quadrants, relative to non-transgenic controls

nervous system

nervous system phenotype ( J:69967 )

N • no differences are seen in volume of dorsal hippocampus or in neuronal cytoarchitecture between transgenic and control mice

amyloid beta deposits ( J:69967 , J:166801 )

• dense-cored amyloid deposits contain amyloid beta-42 peptide (J:69967)

• 14-month old mutants show dense amyloid beta core plaques in the hippocampus (J:166801)

cerebral amyloid angiopathy ( J:69967 )

• by 101 days, plaques are detected within the pial vessels, and in the cerebral vasculature by 196 days

astrocytosis ( J:69967 )

abnormal neurite morphology ( J:69967 )

• amyloid plaques are associated with dystrophic neurites; dystrophic neuron pathology increases with age and frequency of large cored plaques

homeostasis/metabolism

amyloidosis ( J:69967 )

• potent deposition of cerebral amyloid is observed in all mice 90 days of age

amyloid beta deposits ( J:69967 , J:166801 )

• dense-cored amyloid deposits contain amyloid beta-42 peptide (J:69967)

• 14-month old mutants show dense amyloid beta core plaques in the hippocampus (J:166801)

cerebral amyloid angiopathy ( J:69967 )

• by 101 days, plaques are detected within the pial vessels, and in the cerebral vasculature by 196 days

increased creatine level ( J:166801 )

• increase in creatine deposits in the hippocampal gray matter as mutants age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:166801

Genotype
MGI:3722161

tg17

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/0
• Genetic Background: involves: C3H/HeJ * C57BL/6J * FVB/N

mortality/aging

premature death ( J:69967 )

• Background Sensitivity: survival decreases to 25-40% within 120 days of life; only 3/12 mice survive to 365 days

• survival is less than on other genetic backgrounds examined

Genotype
MGI:3665287

tg18

• Allelic Composition: Tg(PRNP-APPSweInd)8Dwst/?
• Genetic Background: involves: 129S6/SvEvTac

nervous system

amyloid beta deposits ( J:113199 )

• observed at 16 and 20 weeks of age in hippocampus and cortex

• level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 16 weeks of age

homeostasis/metabolism

amyloid beta deposits ( J:113199 )

• observed at 16 and 20 weeks of age in hippocampus and cortex

• level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 16 weeks of age

increased circulating triglyceride level ( J:113199 )

• elevated plasma triglyceride levels observed between 9 and 15 weeks of age

increased circulating VLDL triglyceride level ( J:113199 )

• VLDL production rates are increased as early as 9 weeks of age and remain elevated up to 22 weeks of age

• plasma free fatty acid levels were unchanged

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:113199