Phenotypes Associated with This Genotype

Genotype
MGI:6324682

• Allelic Composition: Tg(Thy1-APP*Swe*Ind)fAccu/0
• Genetic Background: involves: C3H * C57BL/6

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

behavior/neurological

abnormal object recognition memory ( J:251735 )

• in the novel object recognition test, mice show a reduced preference for the novel object indicating memory impairment

impaired spatial learning ( J:251735 )

• mice exhibit learning deficits already at 3 months of age, with mice showing increased latency in finding the hidden platform on day 5 of the Morris water maze and perform worse than wild-type mice at 13 months of age

abnormal spatial reference memory ( J:251735 )

• mice show a trend in memory deficit in the Morris water maze at 3 months and significant deficits at 13 months of age, showing a decreased number of passes through the target platform during the probe test

homeostasis/metabolism

amyloid beta deposits ( J:251735 )

• extracellular plaques begin around 4 months of age, mainly in the entorhinal cortex and are well established by 6 months, characterized by mature, neuritic plaques in the entorhinal cortex, subiculum and hippocampus, and in lamina V of the neo-cortex

• plaques spread into outer layers of the cerebral cortex and thalamus by 10 months of age

abnormal enzyme/coenzyme level ( J:251735 )

• insulin degrading enzyme levels are 2.7-fold lower in the cerebral cortex at 3 months of age

• however, levels of neprilysin are unchanged

nervous system

abnormal synaptic bouton morphology ( J:251735 )

• 14 month old mice show lower levels of presynaptic cholinergic boutons in the frontal cortex than in control mice

nervous system inclusion bodies ( J:251735 )

• mice accumulate intracellular amyloid beta oligomers as early as 1 week of age, mainly in neuronal soma and in the initial portion of apical dendrites of pyramidal neurons of lamina V in the cerebral cortex, in pyramidal neurons of CA1 and CA3, subiculum and hilus in the hippocampus and granular neurons of the outer dentate gyrus, in the pyriform cortex and amygdala, in fibers in the alveus and the capsula interna

• by 3 months of age, amyloid beta oligomers are widespread, detectable in pyramidal neurons of laminae III, IV, and VI of the neocortex, the entire hippocampus, amygdala complex, and thalamus

• intracellular Nu1+ soluble, low-n amyloid beta-oligomers appear as soon as 1 week in neuronal compartments of the cerebral cortex and at 1.5 months in the hippocampus

• intracellular OC+ fibrillar oligomers appear as soon as 1 week of age in neuronal compartments of the parietal cortex and at 3 months in the hippocampus

amyloid beta deposits ( J:251735 )

• extracellular plaques begin around 4 months of age, mainly in the entorhinal cortex and are well established by 6 months, characterized by mature, neuritic plaques in the entorhinal cortex, subiculum and hippocampus, and in lamina V of the neo-cortex

• plaques spread into outer layers of the cerebral cortex and thalamus by 10 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:251735