Phenotypes Associated with This Genotype

Genotype
MGI:3693295

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

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

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