Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas Transgene Detail MGI Mouse (MGI:3693208)

Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas
Transgene Detail

Nomenclature

Symbol:	Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas
Name:	transgene insertion 6799, Robert Vassar
MGI ID:	MGI:3693208
Synonyms:	5XFAD, 5XFAD line Tg6799, Tg6799
Transgene:	Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6 x SJL)F1

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	Four familial Alzheimer disease- (FAD-) associated mutations were introduced into a single human amyloid precursor protein cDNA: the "Swedish" double mutation (K670N/M671L); the "Florida" mutation (I716V); and the "London" mutation (V717I). Two FAD-associated mutations, L286V and L286V, likewise were introduced into a human presenilin 1 cDNA. Each cDNA was then cloned independently into the mouse thymus cell antigen 1 gene, replacing a segment that contains thymus-specific elements so that expression of the transgenes is targeted only to the brain. Equal molar amounts of the two transgenes were coinjected into pronuclei of single-celled embryos. (J:32213, J:112949)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 1 strain available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1
behavior/neurological		√
abnormal spatial learning		√
		tg1
immune system		√
brain inflammation		√
		tg1
nervous system		√
brain inflammation		√
abnormal hippocampus morphology		√
decreased pyramidal neuron number		√
abnormal subiculum morphology		√
gliosis		√
astrocytosis		√
abnormal neuron morphology		√
amyloid beta deposits		√
neurodegeneration		√
		tg1
other phenotype		√
amyloid beta deposits		√

		tg1
Disease Models		√
Alzheimer Disease 3		√
Alzheimer Disease; AD		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0

involves: C57BL/6 * SJL

behavior/neurologicalabnormal spatial learning (J:112949)

by 4-5 months of age, defects in Y-maze alternation are detected in transgenic mice, indicating impaired spatial learning/memory

nervous systembrain inflammation (J:112949)

transgenic mice display neuroinflammation

abnormal hippocampus morphology (J:112949)

cortical layer 1 is significantly thinner than in control brains

decreased pyramidal neuron number (J:112949)

large neurons in layer 5 are reduced in number

abnormal subiculum morphology (J:112949)

neurons in subiculum are very pale, or absent

gliosis (J:112949)

microgliosis and astrogliosis is seen in plaque-bearing regions of the brain by 2 months of age; numbers of activated astrocytes and microglia increases with age

astrocytosis (J:112949)

abnormal neuron morphology (J:112949)

some neurons contain intraneuronal aggregates and display disrupted morphology

amyloid beta deposits (J:112949)

mice show Abeta₄₂ deposits at 2 months of age; Abeta₄₀ levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition

amyloid deposition increases rapidly with increasing age

plaques appear first in deep cortical layers and in subiculum, and spread with age to fill most of cortex, subiculum and hippocampus; also, less numerous deposits are observed in thalamus, brainstem and olfactory bulb in older mice

neurodegeneration (J:112949)

synapse degeneration begins at 4 months of age, compared to nontransgenic controls, as shown by reduction in levels of synaptic markers; neurodeneration marker p25 level is ~150% of control at 9 and 12 months

immune systembrain inflammation (J:112949)

transgenic mice display neuroinflammation

other phenotypeamyloid beta deposits (J:112949)

mice show Abeta₄₂ deposits at 2 months of age; Abeta₄₀ levels are lower in amyloid deposits; mice show robust intraneuronal amyloid deposition

amyloid deposition increases rapidly with increasing age

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Alzheimer Disease 3		J:112949
Alzheimer Disease; AD		J:112949

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models involving transgenes or other mutation types.¹
Alzheimer Disease 3 OMIM ID: 607822		tg1	Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas/0	involves: C57BL/6 * SJL	J:112949
Alzheimer Disease; AD OMIM ID: 104300		tg1	Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas/0	involves: C57BL/6 * SJL	J:112949

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Notes

Three transgenic lines coexpressing the APP and PSEN1 proteins at high, medium and low levels, respectively designated Tg6799, Tg7031, and Tg7092, were propagated for analysis, most of which employed Tg6799.

References

Original:	J:112949 Oakley H et al., "Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation." J Neurosci 2006 Oct 4;26(40):10129-40
All:	5 reference(s)

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