Phenotypes Associated with This Genotype

Genotype
MGI:5003501

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

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

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