Phenotypes associated with this allele

• Allele Symbol: Tg(MAPT)8cPdav
• Allele Name: transgene insertion 8c, Peter Davies
• Allele ID: MGI:3057129
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/0	B6.Cg-Tg(MAPT)8cPdav Mapt^tm1(EGFP)Klt/J	MGI:5008417
cx2	App^tm1Ck/App^tm1Ck Psen1^tm1Mpm/Psen1^tm1Mpm Tg(MAPT)8cPdav/0	B6.Cg-Tg(MAPT)8cPdav Psen1^tm1Mpm App^tm1Ck	MGI:5581681
cx3	Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/?	involves: 129S4/SvJae * C57BL/6 * Swiss Webster	MGI:3663749

Genotype
MGI:5008417

cx1

• Allelic Composition: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt; Tg(MAPT)8cPdav/0
• Genetic Background: B6.Cg-Tg(MAPT)8cPdav Mapt^tm1(EGFP)Klt/J

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

Beta-amyloid plaques in Tg(APPswe,PSEN1dE9)85Dbo/0 mice and neurofibrillary tangles in Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/0 mice

behavior/neurological

abnormal spatial learning ( J:172426 )

• 6 month old mutants exhibit slower visuospatial learning than control mice

• in the visuospatial re-learning test performed at 7, 8, 9, and 15 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls

• however, mutants perform better than Tg(APPswe,PSEN1dE9)85Dbo mice on the visuospatial re-learning test at 9 and 18 months of age

taste/olfaction

taste/olfaction phenotype ( J:172426 )

N • mutants do not exhibit Alzheimer's disease-related impairment in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure

nervous system

neurofibrillary tangles ( J:172426 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:172426

Genotype
MGI:5581681

cx2

• Allelic Composition: App^tm1Ck/App^tm1Ck; Psen1^tm1Mpm/Psen1^tm1Mpm; Tg(MAPT)8cPdav/0
• Genetic Background: B6.Cg-Tg(MAPT)8cPdav Psen1^tm1Mpm App^tm1Ck

behavior/neurological

enhanced contextual conditioning behavior ( J:209782 )

• mice show increased contextual freezing frequency at 4 and 12 months of age

• however, cued freezing frequency is unaffected and mice do not exhibit spatial memory deficits in the Morris water maze

increased anxiety-related response ( J:209782 )

• in the elevated plus maze, 4 month old mice spend less time on the open arm, indicating increased anxiety

• however, mice show normal nociception in the hot plate assay

increased fear-related response ( J:209782 )

• mice show slightly higher pre-shock freezing frequency and increased contextual freezing frequency at 4 and 12 months of age, indicating exaggerated fear response

decreased locomotor activity ( J:209782 )

• in the open field, the total travel distance is reduced at 12, but not 4, months of age, indicating age-dependent reduced activity

homeostasis/metabolism

amyloid beta deposits ( J:209782 )

• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age

nervous system

amyloid beta deposits ( J:209782 )

• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age

tau protein deposits ( J:209782 )

• increase in phosphorylated tau in the cortex and hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:209782

Genotype
MGI:3663749

cx3

• Allelic Composition: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt; Tg(MAPT)8cPdav/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * Swiss Webster

nervous system

tau protein deposits ( J:84638 )

• phosphorylated tau accumulates in neuronal cell bodies and dendrites of the hippocampus and neocortex as early as 3 months of age

• in particular, accumulations occur in entorhinal cortex, ventromedial hypothalamus, medial septum and the nucleus of the horizontal limb of the diagonal band

• increase in tau phosphorylation occurs at serine 202, threonine 231 and serine 235 as determined by immunoblot

• tau aggregates in the proximal dendrites have an average width of 15 nm and are not densely packed

• insoluble tau is present in both 2 and 9 month old mice

• paired helical filaments are observed in 9, 12 and 14 month old mice

abnormal neuron morphology ( J:84638 )

• cells in the cortex and hippocampus appear irregularly shaped, often with distorted processes in 13 month old mice

hematopoietic system

abnormal spleen red pulp morphology ( J:174270 )

• splenic red pulp is largely obliterated

abnormal spleen B cell follicle morphology ( J:174270 )

• splenic white pulp contains follicles that are larger and more irregular in shape than normal follicles and are often fused with adjacent follicles

abnormal spleen B cell follicle shape ( J:174270 )

• irregular in shape

increased spleen B cell follicle size ( J:174270 )

immune system

abnormal spleen red pulp morphology ( J:174270 )

• splenic red pulp is largely obliterated

abnormal spleen B cell follicle morphology ( J:174270 )

• splenic white pulp contains follicles that are larger and more irregular in shape than normal follicles and are often fused with adjacent follicles

abnormal spleen B cell follicle shape ( J:174270 )

• irregular in shape

increased spleen B cell follicle size ( J:174270 )

renal/urinary system

abnormal renal glomerulus morphology ( J:174270 )

• kidney glomeruli are dilated probably due to obstruction from the amyloid in the lumen or walls of medullary tubules especially in the papilla

neoplasm

increased lymphoma incidence ( J:174270 )

• malignant lymphoma in the spleen and lymph nodes are seen in some mutants

• megakaryocytes are numerous is some spleens, suggesting a relation to megakaryocytic leukemia

increased follicular lymphoma incidence ( J:174270 )

• splenic architecture is replaced by proliferated immature mononuclear cells arranged in follicular aggregates indicating follicular lymphoma

homeostasis/metabolism

amyloidosis ( J:174270 )

• some mutants older than 18 months exhibit amyloid deposits in the spleen, kidneys, liver, ovary and/or heart

• amyloid is deposited concentrically in the perifollicular sheath, partly or completely encircling the follicles in the spleen

• in the liver, amyloid deposit is in the walls of sinusoids or central veins

• in the kidney, amyloid deposits are seen in the glomeruli

• amyloid deposits in the heart are not composed of amyloid-beta peptide, but rather amyloid A

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:84638 , J:174270