Phenotypes associated with this allele

• Allele Symbol: Tg(Prnp-MAPT*P301L)JNPL3Hlmc
• Allele Name: transgene insertion JNPL3, Mike Hutton
• Allele ID: MGI:3604148
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(APPSWE)2576Kha/0 Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:3720702
tg2	Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:3720701
tg3	Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0	involves: C57BL/6JJcl * DBA/2 * SW	MGI:3714361
tg4	Tg(Prnp-MAPT*P301L)JNPL3Hlmc/?	involves: C57BL/6 * DBA/2	MGI:3722379

Genotype
MGI:3720702

cx1

• 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

Genotype
MGI:3720701

tg2

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

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

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; females develop pathology earlier than males

• levels of soluble endogenous and transgenic Tau protein are similar to double transgenic mice

tau protein deposits ( J:100965 )

gliosis ( J:100965 )

• as severe as astrocytosis seen in Tg(APPSWE)2576Kha Tg(Prnp-MAPT*P301L)JNPL3Hlmc double transgenic mice in ventral diencepalon, hindbrain, and spinal cord

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 )

• granulovacuolar degeneration is seen rarely in neurons of amygdala only

vision/eye

abnormal eye physiology ( J:100965 )

• increased eye irritation

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

Genotype
MGI:3714361

tg3

• Allelic Composition: Tg(Prnp-MAPT*P301L)JNPL3Hlmc/0
• Genetic Background: involves: C57BL/6JJcl * DBA/2 * SW

nervous system

tau protein deposits ( J:100900 )

• tau accumulation is greater in the spinal cord than the cerebellum

abnormal spinal cord morphology ( J:100900 )

• some neuronal loss in the spinal cord is observed

Genotype
MGI:3722379

tg4

• Allelic Composition: Tg(Prnp-MAPT*P301L)JNPL3Hlmc/?
• Genetic Background: involves: C57BL/6 * DBA/2

mortality/aging

premature death ( J:63887 )

• within 3-4 weeks of phenotype onset, mice become moribund

growth/size/body

weight loss ( J:63887 )

• affected animals show decrease in body weight

cachexia ( J:63887 )

• observed in end-stage animals

behavior/neurological

decreased grooming behavior ( J:63887 )

• affected mice display reduction in grooming behavior

limb grasping ( J:63887 )

• 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

decreased grip strength ( J:63887 )

• affected mice fall after grasping rope briefly in hang tests

weakness ( J:63887 )

• after phenotype onset, weakness spreads to all limbs

• affected mice fall after grasping rope briefly in hang tests

abnormal posture ( J:63887 )

• after phenotype onset, mice exhibit dystonic posturing

abnormal locomotor behavior ( J:63887 )

• within 2 weeks of phenotype onset (occurring by 10 months of age), mice cannot ambulate

decreased vocalization ( J:63887 )

• affected mice display reduction in vocalization

nervous system

neurofibrillary tangles ( J:63887 )

• NFT are found in diencephalon, brainstem, cerebellar nuclei, and spinal cord, with 'pre-tangle' pathology observed in cortex neurons, hippocampus, and basal ganglia

gliosis ( J:63887 )

• fibrillary gliosis in anterior horns of spinal cord is seen

• gliosis occurs in brainstem, diencephalon, and basal telencephalon

decreased motor neuron number ( J:63887 )

• motor neuron counts in spinal cord are reduced ~48% from control values

abnormal cranial nerve morphology ( J:63887 )

• cranial nerve nuclei degeneration, including motor nucleus of trigemminal nerve and hypoglossal nerve is observed

muscle

abnormal sarcomere morphology ( J:63887 )

• sarcomeres are disorganized

abnormal skeletal muscle fiber morphology ( J:63887 )

• 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

eye inflammation ( J:63887 )

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

vision/eye

eye inflammation ( J:63887 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
frontotemporal dementia		DOID:9255	OMIM:600274	J:63887