Tg(APPSwe,tauP301L)1Lfa Transgene Detail MGI Mouse (MGI:2672831)

Tg(APPSwe,tauP301L)1Lfa
Transgene Detail

Nomenclature

Symbol:	Tg(APPSwe,tauP301L)1Lfa
Name:	transgene insertion 1, Frank M LaFerla
MGI ID:	MGI:2672831
Synonyms:	3xTg-AD, 3xTgAD, Tg2576/PSEN1
Transgene:	Tg(APPSwe,tauP301L)1Lfa Location: unknown

Transgene
origin

Strain of Origin:

Not Specified

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	To develop a model of Alzheimer's Disease, mice harboring mutant human APP (Swedish double mutation; K670N, M671L) and MAPT (P301L) as well as Psen^tm1Mpm were generated by microinjection of the APP and MAPT transgenic constructs into single cell embryos harvested from mice homozygous for Psen1^tm1Mpm. Southern blot analysis indicated that both transgenic constructs integrated into the same site. Western blot analysis showed APP and MAPT levels to be ~4 fold higher in hemizygous mice and ~6 (APP) to ~7 (Mapt) fold higher homozygous mice, relative to non transgenic mice. Amyloid-Beta peptide (both 40 and 42) was detected in transgenic mice, with greater levels in homozygous mice than in hemizygous mice. Expression was confined to the CNS. Highest steady state levels of proteins were detected in Alzheimer's Disease related regions including the hippocampus and cerebral cortex. Transgenic protein was not detected in the cerebellum. (J:84847)

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	tg2
behavior/neurological		√
abnormal learning/ memory		√
abnormal contextual conditioning behavior		√
		tg1	tg2
nervous system		√	√
amyloid beta deposits		√	√
neurofibrillary tangles			√
		tg1	tg2
other phenotype		√	√
amyloid beta deposits		√	√

		tg1	tg2
Disease Models		√
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

Psen1^tm1Mpm/Psen1^tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa

involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurologicalabnormal learning/ memory (J:99604)

in Morris water mazed, learning of task is normal but retention is impaired; 6-month old mice require 6 days of training to achieve escape latency of >20 seconds, compared to 3 days in 2 month old control mice

at 4 and 6 months, mice show longer escape latencies in the first daily trial relative to the last trial of the previous training day indicating day-to-day retention impairment; 2-month old mice do not show this impairment in retention

short- (1.5 hr posttraining) and long-term (24 hr posttraining) spatial recognition memory in probe trials are impaired at 6 months, whereas 4-month old mice show similar performance at 1.5 hours and impaired retention at 24 hours

after clearance of intraneuronal Abeta using antibodies, early retention deficits are ablated, whereas long-term retention remains impaired

abnormal contextual conditioning behavior (J:99604)

at 6 months, naive and trained mice display significantly impaired long- and short-term retention for contextual fear; at 4 months, mice have normal retention for short-term (1.5 hr) contextual fear but impaired memory of contextual fear at 24 hours

nervous systemamyloid beta deposits (J:99604)

at 6 months, extracellular Abeta plaques are observed in the cerebral cortex, and intracellular accumulation is seen in pyramidal neurons of the CA1 region of hippocampus and within basolateral amygdala and cortical neurons

prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation

treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

other phenotypeamyloid beta deposits (J:99604)

prominent intraneuronal Abeta accumulation is present at 4 months, preceding extracellular amyloid plaque formation

treatment of mice with antibodies to Abeta results in clearance of intraneuroanl Abeta in hippocampus and cortex, but not in amygdala

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Alzheimer Disease; AD		J:99604

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

tg2

Psen1^tm1Mpm/Psen1^tm1Mpm
Tg(APPSwe,tauP301L)1Lfa/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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; AD OMIM ID: 104300		tg1	Psen1^tm1Mpm/Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Tg(APPSwe,tauP301L)1Lfa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	J:99604

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

References

Original:	J:84847 Oddo S et al., "Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction." Neuron 2003 Jul 31;39(3):409-21
All:	45 reference(s)

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