Mouse Genome Informatics
cx1
    Tg(APPSWE)2576Kha/0
Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0

involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• progressive hindlimb weakness is observed

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
• deposits contain both Abeta1-40 and Abeta1-42 peptides
• 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
• 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
• as severe as astrocytosis in ventral diencepalon, hindbrain, and spinal cord
• increase observed in limbic areas with the most NFTs
• 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
• 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
• increased eye irritation

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

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


Mouse Genome Informatics
tg2
    Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0
involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• progressive hindlimb weakness is observed

nervous system
• 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; females develop pathology earlier than males
• levels of soluble endogenous and transgenic Tau protein are similar to double transgenic mice
• as severe as astrocytosis seen in Tg(APPSWE)2576Kha Tg(Prnp-MAPT*P301L)JNPL3Hlmc double transgenic mice in ventral diencepalon, hindbrain, and spinal cord
• 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
• granulovacuolar degeneration is seen rarely in neurons of amygdala only

vision/eye
• increased eye irritation

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


Mouse Genome Informatics
tg3
    Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0
involves: C57BL/6JJcl * DBA/2 * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• tau accumulation is greater in the spinal cord than the cerebellum
• some neuronal loss in the spinal cord is observed


Mouse Genome Informatics
tg4
    Tg(Prnp-MAPT*P301L)JNPL3Hlmc/?
involves: C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• within 3-4 weeks of phenotype onset, mice become moribund

growth/size
• affected animals show decrease in body weight
• observed in end-stage animals

behavior/neurological
• affected mice display reduction in grooming behavior
• at 4.5 months of age, F2 generation mice hold limbs in crossed position rather than extending them when lifted by the tail, and exhibit spontaneous back paw clenching while standing
• at 6.5 months of age, F1 generation mice hold limbs in crossed position rather than extending them when lifted by the tail, and exhibit spontaneous back paw clenching while standing
• affected mice fall after grasping rope briefly in hang tests
• after phenotype onset, weakness spreads to all limbs
• affected mice fall after grasping rope briefly in hang tests
• after phenotype onset, mice exhibit dystonic posturing
• within 2 weeks of phenotype onset (occurring by 10 months of age), mice cannot ambulate
• affected mice display reduction in vocalization

nervous system
• NFT are found in diencephalon, brainstem, cerebellar nuclei, and spinal cord, with 'pre-tangle' pathology observed in cortex neurons, hippocampus, and basal ganglia
• fibrillary gliosis in anterior horns of spinal cord is seen
• gliosis occurs in brainstem, diencephalon, and basal telencephalon
• motor neuron counts in spinal cord are reduced ~48% from control values
• cranial nerve nuclei degeneration, including motor nucleus of trigemminal nerve and hypoglossal nerve is observed

muscle
• sarcomeres are disorganized
• fibers are found in groups of small, acutely angled fibers, indicating neurogenic atrophy
• fibers have increased glycogen and lipofuscin, and redundant basement membranes

immune system
• most mice develop eye irritation and have difficulty in opening their eyes

vision/eye
• most mice develop eye irritation and have difficulty in opening their eyes

Mouse Models of Human Disease
OMIM IDRef(s)
Frontotemporal Dementia; FTD 600274 J:63887