Phenotypes Associated with This Genotype

Genotype
MGI:5553465

• Allelic Composition: Tg(Prnp-APPSweArc)#Rmni/0
• Genetic Background: involves: C57BL/6 * DBA/2

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

behavior/neurological

abnormal learning/memory/conditioning ( J:128080 )

• in the probe trial of the Morris Water Maze, 6 and 9 month old mice spend less time in the goal quadrant and in the goal zone and cross the correct platform position fewer times compared to wild-type mice, indicating impaired memory retention

• however, mice are able to learn the platform position during the acquisition and the reversal training indicating absence of learning deficits

impaired active avoidance behavior ( J:128080 )

• 6 month old mice are highly impaired in the two way active avoidance task

abnormal spatial working memory ( J:128080 )

• in the Y-maze, mutants exhibit reduced percentage of alterations at 6 and 9 months of age, indicating impaired working memory

• however exploration is normal as total number of arm entries is similar to wild-type

increased anxiety-related response ( J:128080 )

• at 6 and 9 months of age, mice show reduced numbers of unprotected head dips indicating increased levels of anxiety

decreased locomotor activity ( J:128080 )

• at 6 and 9 months of age, mice spend less time in the open sectors, indicating an age-dependent decrease in locomotor and exploratory hyperactivity

increased locomotor activity ( J:128080 )

• locomotor and exploratory hyperactivity at 3 months of age in the open field and the zero maze, however this hyperactivity disappears at 6 and 9 months of age

decreased thermal nociceptive threshold ( J:128080 )

• mice show increased sensitivity to heat in the hot plate test

cardiovascular system

abnormal vasodilation ( J:239408 )

• endothelium-dependent, but not smooth muscle-dependent, vasorelaxation is impaired in basilar and femoral arteries of 15, but not 6, month old mice

• dysfunction of the large intracranial, extracerebral arteries is mediated by reduced nitric oxide bioavailability rather than by cerebral amyloid angiopathy

muscle

abnormal vasodilation ( J:239408 )

• endothelium-dependent, but not smooth muscle-dependent, vasorelaxation is impaired in basilar and femoral arteries of 15, but not 6, month old mice

• dysfunction of the large intracranial, extracerebral arteries is mediated by reduced nitric oxide bioavailability rather than by cerebral amyloid angiopathy

nervous system

amyloid beta deposits ( J:128080 , J:203724 )

• intracellular punctate deposits of amyloid deposits in cortical and hippocampal neurons are seen already at 3 months of age and they increase with age, showing a maximum level between 7 and 15 months (J:128080)

• intracellular amyloid beta deposits accumulate outside of the ER (J:128080)

• increase in beta-amyloid plaque deposition, starting around 7 months with dramatic increases in plaques between 9 and 15 months of age (J:128080)

• plaques are characterized by distinct morphology with intensely stained cores surrounded by less dense material and are surrounded by reactive astrocytes and mircoglia (J:128080)

cerebral amyloid angiopathy ( J:128080 , J:203724 , J:239408 )

• mice develop congophilic cerebral beta-amyloid angiopathy, showing beta-amyloid deposits along blood vessel walls accompanied by astrocytosis (J:128080)

• vascular beta-amyloid deposits are spread from the walls over long distances into the adjacent brain parenchyma (J:128080)

• cerebral microbleeds become apparent within 9 months of age and are seen in 71% of mice at 18 months of age compared to 20% of wild-type mice at 21 months of age (J:203724)

• cerebral microbleeds are predominately observed in the cortex, olfactory bulb and in the hippocampus (J:203724)

• parenchymal capillaries, arterioles, and arteries show abundant cerebral amyloid angiopathy (J:239408)

• however, no cerebral amyloid angiopathy or changes in endothelial morphology are seen in the basilar and femoral artery (J:239408)

homeostasis/metabolism

amyloid beta deposits ( J:128080 , J:203724 )

• intracellular punctate deposits of amyloid deposits in cortical and hippocampal neurons are seen already at 3 months of age and they increase with age, showing a maximum level between 7 and 15 months (J:128080)

• intracellular amyloid beta deposits accumulate outside of the ER (J:128080)

• increase in beta-amyloid plaque deposition, starting around 7 months with dramatic increases in plaques between 9 and 15 months of age (J:128080)

• plaques are characterized by distinct morphology with intensely stained cores surrounded by less dense material and are surrounded by reactive astrocytes and mircoglia (J:128080)

cerebral amyloid angiopathy ( J:128080 , J:203724 , J:239408 )

• mice develop congophilic cerebral beta-amyloid angiopathy, showing beta-amyloid deposits along blood vessel walls accompanied by astrocytosis (J:128080)

• vascular beta-amyloid deposits are spread from the walls over long distances into the adjacent brain parenchyma (J:128080)

• cerebral microbleeds become apparent within 9 months of age and are seen in 71% of mice at 18 months of age compared to 20% of wild-type mice at 21 months of age (J:203724)

• cerebral microbleeds are predominately observed in the cortex, olfactory bulb and in the hippocampus (J:203724)

• parenchymal capillaries, arterioles, and arteries show abundant cerebral amyloid angiopathy (J:239408)

• however, no cerebral amyloid angiopathy or changes in endothelial morphology are seen in the basilar and femoral artery (J:239408)

abnormal nitric oxide homeostasis ( J:239408 )

• levels of cyclic GMP are reduced in brain sections containing the basilar artery, indicating a reduced nitric oxide bioavailablity

• however, no differences in oxidative stress are seen in the basilar artery

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:239408
cerebral amyloid angiopathy		DOID:9246		J:203724