Phenotypes Associated with This Genotype

Genotype
MGI:5512698

• Allelic Composition: Tg(APPV717F)109Ili/0; Tg(Prnp-MAPT*P301S)PS19Vle/0
• Genetic Background: involves: C3H * C57BL/6

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

mortality/aging

premature death ( J:165441 )

• median survival of females and males is 12 and 10 months of age, respectively

• mutants exhibit a greater acceleration of death than single Tg(Prnp-MAPT*P301S)PS19Vle mice

growth/size/body

weight loss ( J:165441 )

• decrease in weight with increasing age

• males show a greater decrease in percentage of body weight than females

• mutants exhibit a greater acceleration weight loss than single Tg(Prnp-MAPT*P301S)PS19Vle mice

behavior/neurological

paralysis ( J:165441 )

• 56% of mutants exhibit paresis or paralysis and presence of a hunchback posture at 11 months of age

• males show a more profound motor phenotype than females

• mutants exhibit a greater acceleration of motor phenotype than single Tg(Prnp-MAPT*P301S)PS19Vle mice

paresis ( J:165441 )

• 56% of mutants exhibit paresis or paralysis and presence of a hunchback posture at 11 months of age

nervous system

amyloid beta deposits ( J:165441 )

• limited amyloid beta deposits are seen at 8 months of age within the corpus callosum, stratum oriens, and radiatum of CA1, visual cortex, molecular layer of the dentate gyrus, and retrosplenial area

• at 11 months of age, an increase in amyloid beta deposition is seen in the same areas as at 8 months of age

• mutants exhibit an increase in plaque load with increasing age from 8 to 11 months of age for the anterior and posterior hippocampus

• most amyloid beta deposits are not composed of amyloid beta species that are assembled into ThS-positive amyloid fibrils

neurofibrillary tangles ( J:165441 )

• mutants develop ThS-positive neurofibrillary tangles at a much earlier age than single Tg(Prnp-MAPT*P301S)PS19Vle mice

• a greater proportion of double mutants develop tangles at 8 and 11 months of age than single Tg(Prnp-MAPT*P301S)PS19Vle mice

tau protein deposits ( J:165441 )

• mutants exhibit an accelerated progression in the distribution of abnormally phosphorylated tau from the entorhinal and neocortex, followed by involvement of the hippocampal formation and subcortical structures, to finally penetration of all layers of the neocortex compared to single Tg(Prnp-MAPT*P301S)PS19Vle mice

neurodegeneration ( J:165441 )

• substantial loss of neurons that secrete amyloid beta

skeleton

kyphosis ( J:165441 )

• 56% of mutants exhibit paresis or paralysis and presence of a hunchback posture at 11 months of age

homeostasis/metabolism

amyloid beta deposits ( J:165441 )

• limited amyloid beta deposits are seen at 8 months of age within the corpus callosum, stratum oriens, and radiatum of CA1, visual cortex, molecular layer of the dentate gyrus, and retrosplenial area

• at 11 months of age, an increase in amyloid beta deposition is seen in the same areas as at 8 months of age

• mutants exhibit an increase in plaque load with increasing age from 8 to 11 months of age for the anterior and posterior hippocampus

• most amyloid beta deposits are not composed of amyloid beta species that are assembled into ThS-positive amyloid fibrils

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:165441