Phenotypes Associated with This Genotype

Genotype
MGI:6314698

• Allelic Composition: Tg(APPswe,PSEN1dE9)85Dbo/0
• Genetic Background: involves: C3H/HeH * C57BL/6JNju

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

behavior/neurological

impaired spatial learning ( J:275175 )

• in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice show decreased crossing plate times in the probe trial indicating that spatial discrimination learning impairments begin at 6-7 months of age

abnormal spatial reference memory ( J:275175 )

• in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice require longer to find the platform, indicating that spatial memory impairments begin at 6-7 months of age

abnormal olfactory behavior ( J:275175 )

• in the buried food test, mice need more time to find the hidden food than wild-type mice indicating impaired olfactory performance

• in the olfactory discrimination test, mice show decreases in the numbers of correct olfactory discrimination responses per trial at 3-4 months, 6-7 months, and 9-10 months of age

homeostasis/metabolism

amyloid beta deposits ( J:275175 )

• mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age

nervous system

amyloid beta deposits ( J:275175 )

• mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age

abnormal olfactory bulb granule cell morphology ( J:275175 )

• the dendritic spine density of granule cells is reduced in the olfactory bulb

abnormal olfactory bulb external plexiform layer morphology ( J:275175 )

• mice exhibit a wider synaptic cleft in the external plexiform layer

• however, laminar organization of the olfactory bulb is normal

decreased dendritic spine density ( J:275175 )

• the dendritic spine density of granule cells is reduced in the olfactory bulb

• mature spine density is the same as in wild-type mice at 3-4 months of age but is decreased in 6-7 and 9-10 month old mice

• immature spine density tends to decline at 3-4 and 6-7 months of age and is reduced at 9-10 months of age

abnormal synapse morphology ( J:275175 )

abnormal asymmetric synapse morphology ( J:275175 )

• the presynaptic and postsynaptic membrane structures of asymmetric synapses (excitatory synapses) in the olfactory bulb are damaged

abnormal postsynaptic density morphology ( J:275175 )

• thickness of the postsynaptic density in olfactory bulb asymmetric synapses is thinner in 3-4, 6-7, and 9-10 month old mice

abnormal symmetric synapse morphology ( J:275175 )

• mice exhibit a wider synaptic cleft in the external plexiform layer of symmetric synapses

abnormal synaptic vesicle morphology ( J:275175 )

• synaptic vesicles of olfactory bulb asymmetric synapses exhibit unclear and broken membrane structure and blurred boundaries at 6-7 and 9-10 months of age

abnormal action potential ( J:275175 )

• mitral cells in 3-4 and 9-10 month old mice exhibit a higher spontaneous firing rate of spontaneous action potential indicating the hyperactivation of mitral cells

abnormal synaptic transmission ( J:275175 )

• 3-4 and 9-10 month old mice exhibit increased gamma, low-gamma, and high-gamma oscillations and firing rates of mitral cells in the olfactory bulb external plexiform layer

• local application of the GABA(A)R agonist muscimol nearly abolishes the aberrant increase in gamma oscillations in the external plexiform layer at advanced stages of disease while a GABA(A)R antagonist bicuculline increased the gamma oscillations

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:275175