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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
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (3 available)
Tg(Prnp-MAPT*P301L)JNPL3Hlmc mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• progressive hindlimb weakness is observed (J:100965)
• progressive hindlimb weakness is observed (J:100965)
• reduced (J:100965)
• reduced (J:100965)

nervous system
• 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 (J:100965)
• deposits contain both Abeta1-40 and Abeta1-42 peptides (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 (J:100965)
• deposits contain both Abeta1-40 and Abeta1-42 peptides (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 (J:100965)
• 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 (J:100965)
• norm male animals do not develop enhanced NFT pathology in limbic regions (J:100965)
• 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 (J:100965)
• number and distribution of pretangles is increased in 9-11 month-old mice in limbic areas and cerebral cortex (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 (J:100965)
• 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 (J:100965)
• norm male animals do not develop enhanced NFT pathology in limbic regions (J:100965)
• 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 (J:100965)
• number and distribution of pretangles is increased in 9-11 month-old mice in limbic areas and cerebral cortex (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 (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 (J:100965)
• as severe as astrocytosis in ventral diencepalon, hindbrain, and spinal cord (J:100965)
• as severe as astrocytosis in ventral diencepalon, hindbrain, and spinal cord (J:100965)
• increase observed in limbic areas with the most NFTs (J:100965)
• increase observed in limbic areas with the most NFTs (J:100965)
• Tau filaments occupy large proportion of cell volume, displacing nucleus and cytoplasmic organelles and compressing the Golgi apparatus (J:100965)
• dystrophic neurites reactive for APP epitopes are associated with amyloid plaques (J:100965)
• Tau filaments occupy large proportion of cell volume, displacing nucleus and cytoplasmic organelles and compressing the Golgi apparatus (J:100965)
• dystrophic neurites reactive for APP epitopes are associated with amyloid plaques (J:100965)
• neurofibrillary degeneration resulting from accumulation of NFTs is observed as early as 6 months (J:100965)
• granulovacuolar degeneration is seen in neurons of amygdala, entorhinal cortex, and subiculum of females, characterized by optically clear vacuoles with dense cores (J:100965)
• neurofibrillary degeneration resulting from accumulation of NFTs is observed as early as 6 months (J:100965)
• granulovacuolar degeneration is seen in neurons of amygdala, entorhinal cortex, and subiculum of females, characterized by optically clear vacuoles with dense cores (J:100965)

vision/eye
• increased eye irritation (J:100965)
• increased eye irritation (J:100965)

homeostasis/metabolism
• 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 (J:100965)
• deposits contain both Abeta1-40 and Abeta1-42 peptides (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 (J:100965)
• deposits contain both Abeta1-40 and Abeta1-42 peptides (J:100965)

Mouse Models of Human Disease
OMIM ID Ref(s)
Alzheimer Disease; AD 104300 J:100965


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
02/02/2016
MGI 6.02
The Jackson Laboratory