Tg(PSEN1)5Dbo Transgene Detail MGI Mouse (MGI:2447335)

Tg(PSEN1)5Dbo
Transgene Detail

Nomenclature

Symbol:	Tg(PSEN1)5Dbo
Name:	transgene insertion 5, David R Borchelt
MGI ID:	MGI:2447335
Synonyms:	Hu PS1-A246E, PS1 A246E, PS1-A246E, PS1/A246E, PS1A246E
Transgene:	Tg(PSEN1)5Dbo Location: unknown

Transgene
origin

Strain of Origin:

Not Specified

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene consists of a mouse prion promoter and a cDNA encoding human presenilin 1 bearing the A246E substitution found in familial Alzheimer's disease (FAD). Transgene expression was verified by Northern and Western blot analysis of brain extracts derived from transgenic animals. (J:80882)

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	tg3	tg4
behavior/neurological			√
behavioral despair			√
impaired passive avoidance behavior			√
abnormal discrimination learning			√
abnormal touch/ nociception			√
abnormal nest building behavior			√
		tg1	tg2	tg3	tg4
nervous system		N	√	√	√
nervous system phenotype		N		N	N
amyloid beta deposits			√	√	√
astrocytosis				√
abnormal neuron morphology				√
abnormal neuron physiology				√
		tg1	tg2	tg3	tg4
other phenotype			√	√	√
amyloid beta deposits			√	√	√
		tg1	tg2	tg3	tg4
touch/vibrissae			√
abnormal touch/ nociception			√

		tg1	tg2	tg3	tg4
Disease Models				√
Alzheimer Disease 3				√
Alzheimer Disease 4				√
Alzheimer Disease; AD				√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1

Tg(PSEN1)5Dbo/0

involves: C3H/HeJ * C57BL/6J

tg2

Tg(APP695)3Dbo/0
Tg(PSEN1)5Dbo/0

B6.Cg-Tg(APP695)3Dbo Tg(PSEN1)5Dbo

tg3 Disease Model

Tg(APP695)3Dbo/0
Tg(PSEN1)5Dbo/0

involves: C3H/HeJ * C57BL/6J

nervous systemnervous system phenotype (J:100961)

no differences in neuron number in cingulate cortex relative to wild-type

astrocytosis (J:43788)

associated with dystropic neuritis in cortex and hippocampus

abnormal neuron morphology (J:43788)

dystrophic neuritis associated with reactive gliosis in cortex and hippocampus

amyloid beta deposits (J:43788, J:87691, J:100961)

amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age (J:43788)

amyloid beta peptides AB1-40 and AB1-42 are codeposited (J:43788)

ratio of amyloid beta peptide 40:42 is 1.75:1 (J:87691)

exhibits a 50% increase in amyloid beta peptide 42 (J:87691)

immunoreactive amyloid beta deposits are observed in the cingulate cortex in 12 month-old double transgenic mice; deposits are most evident in gray matter of cingulate and enthorhinal cortex, and to lesser extent in non-neuronal layers of the hippocampal formation (J:100961)

abnormal neuron physiology (J:100961)

neurons in cingulate cortex display 3-fold elevation in phosphorylated tumor suppressor protein (pRb) and activated caspase-3 relative to wild-type neurons

other phenotypeamyloid beta deposits (J:43788, J:87691, J:100961)

amyloid beta deposits found in cortex and hippocampus tissue from 9 and 12 month old mice and increase in number between 10 ans 12 months of age (J:43788)

amyloid beta peptides AB1-40 and AB1-42 are codeposited (J:43788)

ratio of amyloid beta peptide 40:42 is 1.75:1 (J:87691)

exhibits a 50% increase in amyloid beta peptide 42 (J:87691)

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Alzheimer Disease 3		J:43788
Alzheimer Disease 4		J:43788
Alzheimer Disease; AD		J:43788

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

tg4

Tg(APP695)3Dbo/0
Tg(Eno2-PTGS2)32Pasi/0
Tg(PSEN1)5Dbo/0

involves: C3H/HeJ * C57BL/6J

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		tg3	Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0	involves: C3H/HeJ * C57BL/6J	J:43788
Alzheimer Disease 4 OMIM ID: 606889		tg3	Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0	involves: C3H/HeJ * C57BL/6J	J:43788
Alzheimer Disease; AD OMIM ID: 104300		tg3	Tg(APP695)3Dbo/0 Tg(PSEN1)5Dbo/0	involves: C3H/HeJ * C57BL/6J	J:43788

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

Notes

This line was generated from founder number N-5.

Transgenic mice that are also transgenic for Tg(APP695)3Dbo express both human presenilin 1 (A246E variant) and a chimeric amyloid precursor protein (APPSwe) under direction of the mouse prion protein promoter. Elevated levels of the AB1-42(43) peptide are detected in brain homogenates. By nine months of age, histological examination of brain tissue from these mice reveals numerous amyloid deposits resembling those observed in the brains of patients with Alzheimer's disease (AD). The number of amyloid deposits increases dramatically between the ages of 10 and 12 months.

References

Original:	J:80882 Borchelt DR et al., "Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo." Neuron 1996 Nov;17(5):1005-13
All:	27 reference(s)

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