Phenotypes associated with this allele

• Allele Symbol: Tg(Prnp-ITM2B*)1Ruvi
• Allele Name: transgene insertion 1, Ruben Vidal
• Allele ID: MGI:4415606
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Prnp-ITM2B*)1Ruvi/Tg(Prnp-ITM2B*)1Ruvi Tg(Prnp-MAPT*P301L)#Ruvi/Tg(Prnp-MAPT*P301L)#Ruvi	involves: C3HeB/FeJ * C57BL/6	MGI:5525131
tg2	Tg(Prnp-ITM2B*)1Ruvi/Tg(Prnp-ITM2B*)1Ruvi	involves: C3HeB/FeJ * C57BL/6	MGI:5525128
tg3	Tg(Prnp-ITM2B*)1Ruvi/?	B6.C3Fe-Tg(Prnp-ITM2B*)1Ruvi	MGI:4415607

Genotype
MGI:5525131

cx1

• 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

Genotype
MGI:5525128

tg2

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

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, 77% 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, some 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

short stride length ( J:197198 )

growth/size/body

weight loss ( J:197198 )

• weight loss by 6 months of age

nervous system

abnormal astrocyte morphology ( J:197198 )

• increase in expression of glial fibrillary acidic protein, indicating activation of astrocytes

abnormal neurite morphology ( J:197198 )

• presence of clusters of swollen neurites at the periphery of Danish amyloid plaques

• these dystrophic neurites are made up of large and rounded processes

abnormal synapse morphology ( J:197198 )

• with age, synaptophysin levels decrease indicating synaptic degeneration

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

Genotype
MGI:4415607

tg3

• Allelic Composition: Tg(Prnp-ITM2B*)1Ruvi/?
• Genetic Background: B6.C3Fe-Tg(Prnp-ITM2B*)1Ruvi

nervous system

nervous system phenotype ( J:155720 )

N • despite amyloid deposits, no hemorrhages or neurofibrillary tangles are detected

abnormal brain vasculature morphology ( J:155720 )

• vessels show thickened, eosinophilic walls and loss of smooth muscle cells

amyloid beta deposits ( J:155720 , J:155411 )

• both intra- and extra-cellularly throughout the cerebrum cell bodies and dendrites of Purkinje cells (J:155720)

• throughout the cerebellum (J:155411)

cerebral amyloid angiopathy ( J:155720 )

• by 7 months of age consistently seen in pial (leptomeningeal) cerebellar vessels

• by 8-9 months, seen in large and medium-sized parenchymal and penetrating vessels of the cerebrum (neocortex, hippocampus, thalamus and olfactory bulb), the brain stem and the spinal cord

• seen in the walls of large and medium size vessels and in the wall of vessels of the hippocampal fissure

• deposits in the hippocampus are most prominent in the CA3 and CA2 regions and the hilus deposits increase with age

abnormal cerebellar Purkinje cell layer ( J:155720 )

• occasional loss of Purkinje cells in the cerebellum

tau protein deposits ( J:155720 )

• throughout the neuropil of the cerebral cortex and hippocampus

gliosis ( J:155720 )

• severe gliosis

behavior/neurological

abnormal grooming behavior ( J:155720 )

• at 1 year of age

limb grasping ( J:155720 )

• flex their front and hind limbs inward, with paws clasped together and drawn in toward the body

abnormal posture ( J:155720 )

• aged mice (1 year) have an arched back

abnormal gait ( J:155720 )

• aged mice (1 year) walk with a wide-based gait

short stride length ( J:155720 )

• at 1 year of age

cardiovascular system

abnormal brain vasculature morphology ( J:155720 )

• vessels show thickened, eosinophilic walls and loss of smooth muscle cells

homeostasis/metabolism

amyloid beta deposits ( J:155720 , J:155411 )

• both intra- and extra-cellularly throughout the cerebrum cell bodies and dendrites of Purkinje cells (J:155720)

• throughout the cerebellum (J:155411)

cerebral amyloid angiopathy ( J:155720 )

• by 7 months of age consistently seen in pial (leptomeningeal) cerebellar vessels

• by 8-9 months, seen in large and medium-sized parenchymal and penetrating vessels of the cerebrum (neocortex, hippocampus, thalamus and olfactory bulb), the brain stem and the spinal cord

• seen in the walls of large and medium size vessels and in the wall of vessels of the hippocampal fissure

• deposits in the hippocampus are most prominent in the CA3 and CA2 regions and the hilus deposits increase with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cerebral amyloid angiopathy		DOID:9246		J:155720