Tg(Thy1-APPSwDutIowa)BWevn Transgene Detail MGI Mouse (MGI:3721992)

Tg(Thy1-APPSwDutIowa)BWevn
Transgene Detail

Nomenclature

Symbol:	Tg(Thy1-APPSwDutIowa)BWevn
Name:	transgene insertion B, William E Van Nostrand
MGI ID:	MGI:3721992
Synonyms:	APPSwDI, Tg-SwDI, Tg-SwDI/B
Transgene:	Tg(Thy1-APPSwDutIowa)BWevn Location: unknown

Transgene
origin

Strain of Origin:

C57BL/6

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	A transgenic construct containing 2.1kb of the human amyloid beta-precursor protein, APP gene, 770 isoform, with the Swedish K670N/M671L, Dutch E693Q and Iowa D694N mutations, under the control of the mouse thymus cell antigen 1, theta, Thy1, promoter was injected into fertilized C57BL/6 mouse eggs. Founder line B was subsequently established and homozygotes generated. Human amyloid beta precursor protein expression is detected in the brains of transgenic mice. Two other lines, A anc C were also generated, with line A having similar levels of transgene expression and amyloid beta accumulation to line B while line C has 2-fold higher expression of human Amyloid beta-precursor protein and shows 4-fold higher accumulations of soluble and insoluble AB peptides in the brain. (J:89848)

Find Mice (IMSR)

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

Carrying this Mutation:

Mouse Strains: 2 strains 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
cardiovascular system		√
abnormal blood circulation		√
		tg1	tg2	tg3	tg4
hematopoietic system			√	√
abnormal microglial cell morphology			√	√
		tg1	tg2	tg3	tg4
immune system		√	√	√
abnormal microglial cell physiology		√
abnormal microglial cell morphology			√	√
		tg1	tg2	tg3	tg4
nervous system		√	√	√	√
abnormal microglial cell physiology		√
cerebral amyloid angiopathy		√
abnormal astrocyte morphology		√	√	√
amyloid beta deposits		√	√	√	√
abnormal microglial cell morphology			√	√
abnormal hippocampus CA3 region morphology					√
abnormal subiculum morphology					√
loss of hippocampal neurons					√
decreased neuron number					√
decreased interneuron number					√
		tg1	tg2	tg3	tg4
other phenotype		√	√	√	√
amyloidosis		√
cerebral amyloid angiopathy		√
amyloid beta deposits		√	√	√	√

		tg1	tg2	tg3	tg4
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

Tg(Thy1-APPSwDutIowa)BWevn/0

involves: C57BL/6

nervous systemabnormal microglial cell physiology (J:124911)

activation of microglial and astrocytes is elevated in cortex

microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

cerebral amyloid angiopathy (J:89848, J:124911)

levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (J:89848)

vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta deposits in and around microvessels in the thalamus and subiculum are observed (J:89848)

microvascular amyloid beta accumulations are mainly fibrillar (J:89848)

some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (J:89848)

evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (J:89848)

microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (J:124911)

abnormal astrocyte morphology (J:124911)

astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent

amyloid beta deposits (J:89848, J:124911)

over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months (J:89848)

soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (J:89848)

amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (J:89848)

parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (J:89848)

deposits are largely in parenchyma and in diffuse form in cortex (J:124911)

immune systemabnormal microglial cell physiology (J:124911)

activation of microglial and astrocytes is elevated in cortex

microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

other phenotypeamyloidosis (J:89848)

mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta

cerebral amyloid angiopathy (J:89848, J:124911)

microvascular amyloid beta accumulations are mainly fibrillar (J:89848)

evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (J:89848)

microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (J:124911)

amyloid beta deposits (J:89848, J:124911)

soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (J:89848)

parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (J:89848)

deposits are largely in parenchyma and in diffuse form in cortex (J:124911)

cardiovascular systemabnormal blood circulation (J:119251)

reduced cerebral blood flow, CBF, response (21% increase) to whisker stimulation is observed relative to controls (38% increase) at 9 months

with myocardin gene transfer, CBF response drops to 10% in transgenic mice, a decrease of 50%, while it increased to 27% with shSRF gene transfer compared to 19% in shGFP controls

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Alzheimer Disease; AD		J:89848

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

tg2

Apoe^{tm2(APOE*3)Mae}/Apoe^{tm2(APOE*3)Mae}
Tg(Thy1-APPSwDutIowa)BWevn/?

involves: 129P2/OlaHsd * C57BL/6

tg3 Disease Model

Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}
Tg(Thy1-APPSwDutIowa)BWevn/?

involves: 129P2/OlaHsd * C57BL/6

tg4

Nos2^tm1Lau/Nos2^tm1Lau
Tg(Thy1-APPSwDutIowa)BWevn/?

involves: 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		tg3	Apoe^{tm3(APOE4)Mae}/Apoe^{tm3(APOE4)Mae} Tg(Thy1-APPSwDutIowa)BWevn/?	involves: 129P2/OlaHsd * C57BL/6	J:136318
		tg1	Tg(Thy1-APPSwDutIowa)BWevn/0	involves: C57BL/6	J:89848

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

References

Original:	J:89848 Davis J et al., "Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor." J Biol Chem 2004 May 7;279(19):20296-306
All:	17 reference(s)

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
Citing These Resources Funding Information Warranty Disclaimer & Copyright Notice Send questions and comments to User Support.	last database update 11/20/2009 MGI_4.31 Web browser compatibility