Phenotypes Associated with This Genotype

Genotype
MGI:3663749

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

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

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