Phenotypes Associated with This Genotype

Genotype
MGI:4452488

• Allelic Composition: Tg(Prnp-ITM2B*)7Jckr/0
• Genetic Background: C57BL/6-Tg(Prnp-ITM2B*)7Jckr

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

behavior/neurological

behavior/neurological phenotype ( J:159279 )

N • at 6 months, mice exhibit normal behavior

abnormal spatial learning ( J:159279 )

• at 18 to 20 months, mice take longer to find the platform in the Morris water maze compared with wild-type mice

• during the probe trials, 18 to 20 month old mice tend to have a preference for the training target zone compared with wild-type mice

• during the two probe trials, mice exhibit a minor reduction in searching precision after 24 hours and a total loss of spatial selectivity after 6 days compared with wild-type mice

behavioral despair ( J:159279 )

• in Morris water maze, aged mice exhibit increased passive floating and reduced swim speed compared with wild-type mice

increased anxiety-related response ( J:159279 )

• in an open field test, aged mice exhibit reduced activity, preference for the wall zone, reduced vertical activity, and more numerous fecal boli compared with wild-type mice

increased thigmotaxis ( J:159279 )

• in Morris water maze and in an open field tests with aged mice

impaired swimming ( J:159279 )

• in Morris water maze, aged mice exhibit increased passive floating and reduced swim speed compared with wild-type mice

decreased vertical activity ( J:159279 )

• in an open field test with aged mice

decreased locomotor activity ( J:159279 )

• in an open field test with aged mice

nervous system

abnormal brain vasculature morphology ( J:159279 )

• at 18 months, mice exhibit age-dependent, vasculature-associated Dan-amyloid deposition in the amygdala, thalamus, brainstem, and cerebellum unlike wild-type mice

• smaller vessels are often obstructed by depositions

• perivascular plaques often surround a significant portion of the vessel surface

• 18 month old mice exhibit cerebral microhemorrhages unlike in wild-type mice

intracerebral hemorrhage ( J:159279 )

• 18 month old mice exhibit cerebral microhemorrhages unlike in wild-type mice

microgliosis ( J:159279 )

• in juxtaposition to amyloid depositions

abnormal hippocampus neuron morphology ( J:159279 )

• neuronal cell bodies in the CA3/4 region of the hippocampus are displaced compared to in wild-type mice

astrocytosis ( J:159279 )

• Dan-amyloid deposition elicits activation of astrocytes throughout the entire brain

abnormal neurite morphology ( J:159279 )

• mice exhibit dystrophic neurites unlike wild-type mice

abnormal synaptic bouton morphology ( J:159279 )

• Dan-amyloid lesions are associated with dystrophic boutons

cardiovascular system

abnormal brain vasculature morphology ( J:159279 )

• at 18 months, mice exhibit age-dependent, vasculature-associated Dan-amyloid deposition in the amygdala, thalamus, brainstem, and cerebellum unlike wild-type mice

• smaller vessels are often obstructed by depositions

• perivascular plaques often surround a significant portion of the vessel surface

• 18 month old mice exhibit cerebral microhemorrhages unlike in wild-type mice

intracerebral hemorrhage ( J:159279 )

• 18 month old mice exhibit cerebral microhemorrhages unlike in wild-type mice

growth/size/body

decreased body weight ( J:159279 )

• at 18 months, mice are 20% to 30% lighter than wild-type mice

slow postnatal weight gain ( J:159279 )

• coinciding with Dan-amyloid accumulation

skeleton

kyphosis ( J:159279 )

• at 18 months

hematopoietic system

microgliosis ( J:159279 )

• in juxtaposition to amyloid depositions

immune system

microgliosis ( J:159279 )

• in juxtaposition to amyloid depositions

integument

alopecia ( J:159279 )

• at 18 months

homeostasis/metabolism

amyloidosis ( J:159279 )

• at 18 months, mice exhibit age-dependent, vasculature-associated Dan-amyloid deposition in the amygdala, thalamus, brainstem, and cerebellum unlike wild-type mice

• smaller vessels are often obstructed by depositions

• perivascular plaques often surround a significant portion of the vessel surface

• perivascular amyloid penetrates into the surrounding parenchyma and is surrounded by microglia and dystrophic neurites

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral amyloid angiopathy		DOID:9246		J:159279