Phenotypes Associated with This Genotype

Genotype
MGI:3720702

• Allelic Composition: Tg(APPSWE)2576Kha/0; Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0
• Genetic Background: involves: C57BL/6 * DBA/2 * SJL * SW

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

behavior/neurological

decreased grooming behavior ( J:100965 )

hunched posture ( J:100965 )

paraparesis ( J:100965 )

• progressive hindlimb weakness is observed

decreased vocalization ( J:100965 )

• reduced

nervous system

amyloid beta deposits ( J:100965 )

• mice have amyloid plaques similar in number and distribution to Tg(APPSWE)2576Kha mice; plaques are detected as early as 6 months, but do become numerous only in older mice (8.5 to 15 months) in the olfactory cortex, cingulated gyrus, amygdala, entorhinal cortex, and hippocampus

• deposits contain both Abeta1-40 and Abeta1-42 peptides

neurofibrillary tangles ( J:100965 )

• by 3 months of age, neurofibrillary tangles (NFTs) composed of straight fibers sometimes forming complex structures are detected in the spinal cords and pons of transgenic animals, and become more numerous with age

• older females 9-11 months of age display marked increases in NFTs in limbic areas, such as the olfactory cortex, entorhinal cortex, and amygdala; density of NFTs in females is >7-fold higher than in Tg(Prnp-MAPT*P301L)JNPL3 littermates

• norm male animals do not develop enhanced NFT pathology in limbic regions

• NFTs are also found in subiculum, hippocampus and sometimes in the isocortex, whereas NFTs are never or rarely observed in these brain regions of Tg(Prnp-MAPT*P301L)JNPL3 animals

• number and distribution of pretangles is increased in 9-11 month-old mice in limbic areas and cerebral cortex

tau protein deposits ( J:100965 )

• levels of soluble endogenous and transgenic Tau protein are similar to Tg(Prnp-MAPT*P301L)JNPL3Hlmc transgenic mice; 64-kd insoluble tau species in increased in cortex/limbic regions of females 9-11 months compared to Tg(Prnp-MAPT*P301L)JNPL3Hlmc mice

gliosis ( J:100965 )

• as severe as astrocytosis in ventral diencepalon, hindbrain, and spinal cord

astrocytosis ( J:100965 )

• increase observed in limbic areas with the most NFTs

abnormal neuron morphology ( J:100965 )

• Tau filaments occupy large proportion of cell volume, displacing nucleus and cytoplasmic organelles and compressing the Golgi apparatus

• dystrophic neurites reactive for APP epitopes are associated with amyloid plaques

neuron degeneration ( J:100965 )

• neurofibrillary degeneration resulting from accumulation of NFTs is observed as early as 6 months

• granulovacuolar degeneration is seen in neurons of amygdala, entorhinal cortex, and subiculum of females, characterized by optically clear vacuoles with dense cores

vision/eye

abnormal eye physiology ( J:100965 )

• increased eye irritation

homeostasis/metabolism

amyloid beta deposits ( J:100965 )

• mice have amyloid plaques similar in number and distribution to Tg(APPSWE)2576Kha mice; plaques are detected as early as 6 months, but do become numerous only in older mice (8.5 to 15 months) in the olfactory cortex, cingulated gyrus, amygdala, entorhinal cortex, and hippocampus

• deposits contain both Abeta1-40 and Abeta1-42 peptides

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:100965