Phenotypes Associated with This Genotype

Genotype
MGI:5525131

• Allelic Composition: Tg(Prnp-ITM2B*)1Ruvi/Tg(Prnp-ITM2B*)1Ruvi; Tg(Prnp-MAPT*P301L)#Ruvi/Tg(Prnp-MAPT*P301L)#Ruvi
• Genetic Background: involves: C3HeB/FeJ * C57BL/6

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

mortality/aging

premature death ( J:197198 )

• reduction in survival rate beginning around 9 months of age

growth/size/body

weight loss ( J:197198 )

• weight loss by 6 months of age to similar extent as in either single mutant mice

behavior/neurological

abnormal grooming behavior ( J:197198 )

• abnormal grooming behavior starting around 9 months of age as evident by dull rough coats

limb grasping ( J:197198 )

• at 12 months of age, 88% of mutants exhibit cupping of the hind paws and bilaterally pulling of the hind paws toward the abdomen when suspended by the tail compared to 33% of wild-type mice

hunched posture ( J:197198 )

• by 12 months of age, mutants show a hunched back or arched posture when sitting and walking

abnormal gait ( J:197198 )

• 12 month old mutants exhibit an usual gait in which the mouse holds its body near the walking surface and takes wide shortened steps

immune system

increased inflammatory response ( J:197198 )

• expression analysis indicates neuroinflammation, with activated astrocytes and microglia seen in close proximity of amyloid deposits and neurofibrillary tangles; activated microglia are seen before Danish amyloid deposition and correlates with tau deposition

nervous system

amyloid beta deposits ( J:197198 )

• beginning around 6-7 months of age, mutants show amyloid deposition primarily in leptomeningeal cerebellar vessels and later developing extensive amyloid lesions in the parenchyma and vasculature of the neocortex, hippocampus, and cerebellum

• parenchymal amyloid deposition is most prominent in the CA3 and CA2 regions and the hilus of the hippocampus

neurofibrillary tangles ( J:197198 )

tau protein deposits ( J:197198 )

• tau deposits are predominately seen in the hippocampus, piriform cortex, brain stem, spinal cord, and the cerebellum

• tau accumulation is enhanced compared to single Tg(Prnp-MAPT*P301L)#Ruvi mice that occurs before extracellular deposition of Danish amyloid plaques

abnormal synapse morphology ( J:197198 )

• by 6 months of age, synaptophysin levels are decreased, indicating synaptic degeneration; this is seen earlier and with a more severe loss of synaptophysin than in either single mutant and occurs before the detection of amyloid plaques or tau pathology

homeostasis/metabolism

amyloid beta deposits ( J:197198 )

• beginning around 6-7 months of age, mutants show amyloid deposition primarily in leptomeningeal cerebellar vessels and later developing extensive amyloid lesions in the parenchyma and vasculature of the neocortex, hippocampus, and cerebellum

• parenchymal amyloid deposition is most prominent in the CA3 and CA2 regions and the hilus of the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral amyloid angiopathy		DOID:9246		J:197198