Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-APP^SL)28Lpr
• Allele Name: transgene insertion 28, Laurent Pradier
• Allele ID: MGI:3510606
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Psen1^tm1Lpr/Psen1^tm1Lpr Tg(Thy1-APP^SL)28Lpr/0	either: 129/Sv or (involves: 129/Sv * C57BL/6)	MGI:3510652
cx2	Psen1^tm1Lpr/Psen1^tm1Lpr Tg(Thy1-APP^SL)28Lpr/0	involves: 129 * C57BL/6 * CBA	MGI:5003501
cx3	Tg(Hmgcr-PSEN1*M146L)#Lpr/0 Tg(Thy1-APP^SL)28Lpr/0	involves: C57BL/6 * CBA	MGI:5003459
tg4	Tg(Thy1-APP^SL)28Lpr/0	B6.Cg-Tg(Thy1-APP^SL)28Lpr	MGI:5003504
tg5	Tg(Thy1-APP^SL)28Lpr/0	involves: C57BL/6 * CBA	MGI:5003460

Genotype
MGI:3510652

cx1

• Allelic Composition: Psen1^tm1Lpr/Psen1^tm1Lpr; Tg(Thy1-APP^SL)28Lpr/0
• Genetic Background: either: 129/Sv or (involves: 129/Sv * C57BL/6)

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

nervous system

amyloid beta deposits ( J:93770 )

• accelerated rate of A-beta deposition starting at 2.5 months of age

• by 6 months of age deposition has become widespread and numerous in cortical, hippocampal and thalamic areas

• astrocytic and microglial activation around amyloid plaques

abnormal hippocampus pyramidal cell layer ( J:93770 )

• marked reduction in thickness of the hippocampal pyramidal cell layer by 10 months of age

• no amyloid plaques in the CA1/2 pyramidal cell layer

homeostasis/metabolism

amyloid beta deposits ( J:93770 )

• accelerated rate of A-beta deposition starting at 2.5 months of age

• by 6 months of age deposition has become widespread and numerous in cortical, hippocampal and thalamic areas

• astrocytic and microglial activation around amyloid plaques

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:93770
Alzheimer's disease 3		DOID:0110042	OMIM:607822	J:93770

Genotype
MGI:5003501

cx2

• Allelic Composition: Psen1^tm1Lpr/Psen1^tm1Lpr; Tg(Thy1-APP^SL)28Lpr/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:128106 , J:128243 , J:139736 , J:146342 )

• some plaques are detected at 2 months of age in the cervical spinal cord and plaques increase with age (J:128106)

• plaque formation is higher in the cervical spinal cord compared to the thoracic and lumbar regions (J:128106)

• plaques are almost exclusively found in the gray matter (J:128106)

• amyloid plaques are located frequently within the granular cell layer of the dentate gyrus (J:139736)

• significant plaque formation is detected in the frontal cortex by 2 months of age (J:146342)

• from 6 to 12 months of age plaques become more densely packed (J:146342)

abnormal thalamus morphology ( J:146342 )

• amyloid beta plaques form but no intracellular aggregates are seen

• numerous plaques form between 2 and 6 months of age and the pathology increases with age

• unlike in the frontal cortex, no neuronal loss is detected in the thalamus

abnormal hippocampus morphology ( J:139736 )

abnormal dentate gyrus morphology ( J:139736 )

• the granule cell layer is less densely packed at 12 months of age compared to 2 months of age

• the granule cell border is often frayed

• ectopic cells that are often orientated towards extracellular amyloid deposits can be detected at 2 months of age

• amyloid plaques are located frequently within the granular cell layer of the dentate gyrus

• decrease in the number of dentate gyrus granule cells at 12 months of age

abnormal hippocampus granule cell morphology ( J:139736 )

• decrease in the number of dentate gyrus granule cells at 12 months of age

abnormal frontal lobe morphology ( J:146342 )

• massive intra- and extra-cellular amyloid beta deposits are detected in the frontal cortex at as early as 1.5 months of age, before significant plaque formation is detected

• by 6 months of age intracellular accumulations are no longer a prominent pathological feature

• a 28% and 35% loss of neurons is seen in the frontal cortex at 6 and 12 months of age, respectively, compared to age-matched controls

• frontal cortex volume is reduced compared to controls at 6 and 12 months of age

abnormal neurite morphology ( J:128106 )

• thickened and irregularly shaped neurites are seen in the medulla at 14 months of age

abnormal axon morphology ( J:128106 )

• axonal spheroids are detected in pons and cortical areas at 6 months of age and in the spinal cord mostly along the anterior margin of the ventral horn and less frequently in the intermediolateral and dorsal horn

• at 10 and 14 months of age axonal spheroids are detected in pons, cortex, medulla, midbrain, hippocampus, corpus callosum and striatum

• larger axonal varicosities are seen in the medulla at 14 months of age

• large axonal dilatations are localized in white matter fiber tracts in close vicinity to the ventral horn in the spinal cord

abnormal myelin sheath morphology ( J:128106 )

• dilated axons often display thinned or focally absent myelin sheaths

• increased deposition of myelin ovoids in the white matter

decreased neuron number ( J:146342 )

• a 28% and 35% loss of neurons is seen in the frontal cortex at 6 and 12 months of age, respectively, compared to age-matched controls

homeostasis/metabolism

amyloid beta deposits ( J:128106 , J:128243 , J:139736 , J:146342 )

• some plaques are detected at 2 months of age in the cervical spinal cord and plaques increase with age (J:128106)

• plaque formation is higher in the cervical spinal cord compared to the thoracic and lumbar regions (J:128106)

• plaques are almost exclusively found in the gray matter (J:128106)

• amyloid plaques are located frequently within the granular cell layer of the dentate gyrus (J:139736)

• significant plaque formation is detected in the frontal cortex by 2 months of age (J:146342)

• from 6 to 12 months of age plaques become more densely packed (J:146342)

decreased circulating cholesterol level ( J:128243 )

• significant decrease in plasma cholesterol between 2 and 6 months of age that is not seen in wild-type controls or either single transgenic mice

increased circulating cholesterol level ( J:128243 )

• basal cholesterol levels are increase compared to wild-type controls probably as a result of differences in strain background

behavior/neurological

limb grasping ( J:128106 )

• at 10 and 14 months of age

impaired coordination ( J:128106 )

• impaired performance in a balance beam test at 10 and 14 months of age

growth/size/body

decreased body weight ( J:128106 )

• at 10 and 14 months of age compared to mutant mice not carrying the transgene

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:128106

Genotype
MGI:5003459

cx3

• Allelic Composition: Tg(Hmgcr-PSEN1*M146L)#Lpr/0; Tg(Thy1-APP^SL)28Lpr/0
• Genetic Background: involves: C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:86694 , J:99507 , J:128243 )

• plaques are seen at 6 months of age (J:86694)

• detected in the hippocampus at 4.5 and 17 months of age (J:99507)

• abundant amyloid beta neuropil deposits in hippocampal and cortical areas in aged mice (J:128243)

decreased brain size ( J:108853 )

• non-corrected intracranial and brain volumes are reduced compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics at 10 weeks of age

• corrected brain volumes are strongly decreased with age

decreased brain weight ( J:108853 )

• in aged mice compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics

increased brain size ( J:108853 )

• significant increase in brain length with age compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics

abnormal brain internal capsule morphology ( J:108853 )

• surface area of the internal capsule does not increase with age unlike in Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics

abnormal telencephalon morphology ( J:108853 )

decreased corpus callosum size ( J:108853 )

• decrease in thickness of the caudal corpus callosum with age

decreased hippocampal fornix size ( J:108853 )

• decrease in fornix diameter in aged mice

abnormal hippocampus layer morphology ( J:99507 )

• age-related decline in mean synaptic bouton densities within the stratum lucidum of area CA3

abnormal hippocampus molecular cell layer ( J:99507 )

• age-related decline in mean synaptic bouton densities and in mean volume

abnormal hippocampus stratum radiatum morphology ( J:99507 )

• age-related decline in mean synaptic bouton densities in area CA1?2

abnormal neurite morphology ( J:86694 )

• clusters of swollen and abnormally distorted neuritic profiles are seen

abnormal synaptic bouton morphology ( J:99507 )

• age-related decline in mean synaptic bouton densities within the hippocampal molecular cell layer, stratum lucidum of area CA3, and stratum radiatum of area CA1?2

abnormal nervous system physiology ( J:108853 )

• global brain atrophy in aged mice

homeostasis/metabolism

amyloid beta deposits ( J:86694 , J:99507 , J:128243 )

• plaques are seen at 6 months of age (J:86694)

• detected in the hippocampus at 4.5 and 17 months of age (J:99507)

• abundant amyloid beta neuropil deposits in hippocampal and cortical areas in aged mice (J:128243)

decreased circulating cholesterol level ( J:128243 )

• significant decrease in plasma cholesterol between 3 and 13 months of age that is not seen in wild-type controls

• plasma cholesterol levels are reduced compared to wild-type controls at 13 months of age but not at 3 months of age

growth/size/body

abnormal body size ( J:108853 )

• brain weight to body weight ratio is increased compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics at 24 months of age

decreased body weight ( J:108853 )

• in aged mice compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:86694 , J:99507

Genotype
MGI:5003504

tg4

• Allelic Composition: Tg(Thy1-APP^SL)28Lpr/0
• Genetic Background: B6.Cg-Tg(Thy1-APP^SL)28Lpr

mortality/aging

premature death ( J:145588 )

• enhanced lethality at young ages (less than 4 months of age)

behavior/neurological

increased anxiety-related response ( J:145588 )

• spend more time in the closed arms of an elevated plus maze at 15 months of age compared to age matched controls

impaired coordination ( J:145588 )

• cross fewer segments and show a reduced latency to fall in a stationary beam test at 15 months of age

decreased grip strength ( J:145588 )

• significant decrease in latency to fall in a wire grid assay at 3 and 15, but not at 6, months of age

• significant decrease in latency to fall in a coat hanger assay at 15 months of age

decreased locomotor activity ( J:145588 )

• at 3, 6, and 15 months of age in an open field test

• activity decreases with age

nervous system

amyloid beta deposits ( J:145588 )

increased brain size ( J:145588 )

• increase in brain length but not weight

growth/size/body

decreased body weight ( J:145588 )

• from 3 to 15 months of age

homeostasis/metabolism

amyloid beta deposits ( J:145588 )

Genotype
MGI:5003460

tg5

• Allelic Composition: Tg(Thy1-APP^SL)28Lpr/0
• Genetic Background: involves: C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:86694 , J:99507 )

• plaques are seen at 6 months of age (J:86694)

• detected in the hippocampus at 17 months of age (J:99507)

abnormal brain morphology ( J:95529 )

• levels of SDS-soluble amyloid beta protein are higher in females than in males at 3 months of age

abnormal hippocampus molecular cell layer ( J:99507 )

• age-related decline in mean synaptic bouton densities

abnormal hippocampus stratum radiatum morphology ( J:99507 )

• age-related decline in mean synaptic bouton densities in area CA1?2

abnormal neurite morphology ( J:86694 )

• clusters of swollen and abnormally distorted neuritic profiles are seen

abnormal synaptic bouton morphology ( J:99507 )

• age-related decline in mean synaptic bouton densities within the hippocampal molecular cell layer and stratum radiatum of area CA1?2

abnormal nervous system physiology ( J:95529 )

• elevated levels of lipid peroxidation products in brain homogenates in females at 3 months of age and in males and females at 12 months of age

• reduced levels of antioxidant enzymes at 3 and 12 months of age

abnormal neuron physiology ( J:152956 )

• impaired mitochondrial function

cellular

abnormal mitochondrial ATP synthesis coupled electron transport ( J:152956 )

• mitochondrial membrane potentials and ATP levels are reduced in dissociated brain cells at 3 months of age

• inhibition of complex IV and significantly reduced cytochrome c oxidase activity in cerebral isolated mitochondria

• state 3 and state 4 respiration are significantly reduced in freshly isolated cerebral mitochondria at 17 months of age

homeostasis/metabolism

amyloid beta deposits ( J:86694 , J:99507 )

• plaques are seen at 6 months of age (J:86694)

• detected in the hippocampus at 17 months of age (J:99507)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:86694 , J:99507