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| These transgenic mice express 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. Plaque-like deposits of amyloid beta that are similar to the plaques observed in human patients with the Dutch and Iowa familial disorders, are initially detected at approximately three months of age in the subiculum, hippocampus and cortex. Amyloid beta deposits are detected throughout the forebrain by 12 months of age. This mutant mouse strain may be useful in studies of Alzheimer's disease. | |||||||||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 10-MAR-09 Species laboratory mouse Generation F?+1F4 (18-NOV-09) Donating Investigator William Van Nostrand, Stony Brook University Description
These transgenic mice express neuronally derived human amyloid beta-precursor protein, APP gene, 770 isoform, containing the Swedish K670N/M671L, Dutch E693Q and Iowa D694N mutations, under the control of the mouse thymus cell antigen 1, theta, Thy1, promoter. Mice hemizygous for the transgenic insert exhibit expression of human amyloid beta precursor protein in the cortex, hippocampus and brain stem with lower expression detected in the cerebellum. At age three months hemizygotes show a progressive accumulation of insoluble amyloid beta 40 and 42 peptides in brain tissue. The levels of accumulation of amyloid beta peptides is 12 to 14 fold higher in brain microvessels than in whole forebrain tissue homogenates. Fibrillar microvascular accumulations of amyloid beta peptides begin at approximately six months of age. Diffuse plaque-like deposits of amyloid beta that are similar to the plaques observed in human patients with the Dutch and Iowa familial disorders are initially detected at approximately 3 months of age in the subiculum, hippocampus and cortex. After six months of age the diffuse plaque-like deposits increase in number and spread to the olfactory bulb and thalamic region. Amyloid beta deposits are detected throughout the forebrain by 12 months of age. The donating investigator has made the strain homozygous and reports that mice homozygous for the transgenic insert are viable and fertile. This mutant mouse strain may be useful in studies of Alzheimer's disease and cerebral amyloid angiopathy.Development
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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying Tg(Thy1-APPSwDutIowa)BWevn allele
009126 B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/J View Strains carrying Tg(Thy1-APPSwDutIowa)BWevn (1 strain)
008609 129S1.129(Cg)-Tg(APPSw)40Btla/2J 006409 129S1.129(Cg)-Tg(APPSw)40Btla/J 006555 A.129(B6)-Tg(APPSw)40Btla/J 005300 B6.129-Tg(APPSw)40Btla/J 005301 B6.129S2-Tg(APP)8.9Btla/J 006406 B6.129S4-Tg(APPSwLon)96Btla/J 005864 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J 004662 B6.Cg-Tg(PDGFB-APP)5Lms/J 006293 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2J 006006 B6.Cg-Tg(Prnp-APP)A-2Dbo/J 006005 B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/J 007049 B6.Cg-Tg(tetO-APPSwInd)885Dbo/J 004462 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J 006004 B6C3-Tg(tetO-APPSwInd)885Dbo/J 006472 D2.129(B6)-Tg(APPSw)40Btla/J
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
assigned by genotype
Tg(Thy1-APPSwDutIowa)BWevn/0
involves: C57BL/6
- nervous system phenotype
- abnormal astrocyte morphology (MGI Ref ID J:124911)
- astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent
- abnormal microglial cell physiology (MGI Ref ID J:124911)
- activation of microglial and astrocytes is elevated in cortex
- microglial cells show significantly increased levels of complement proteins C1q, C3 and C4
- amyloid beta deposits (MGI Ref ID J:89848)
- 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
- soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels
- 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
- parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature
- deposits are largely in parenchyma and in diffuse form in cortex
- cerebral amyloid angiopathy (MGI Ref ID J:89848)
- 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
- 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
- microvascular amyloid beta accumulations are mainly fibrillar
- 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
- evidence of microhemorrhage is observed in microvessels with amyloid beta deposits
- microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions
- immune system phenotype
- abnormal complement physiology (MGI Ref ID J:124911)
- in thalamus, hippocampus and subiculum, increased levels of 3 early complement components C1q, C3, and C4, are detected compared to control animals
- increased levels of synthesis of complement proteins is found in cortical and thalamic regions of transgenic brains
- abnormal microglial cell physiology (MGI Ref ID 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 phenotype
- amyloidosis (MGI Ref ID J:89848)
- mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta
- amyloid beta deposits (MGI Ref ID J:89848)
- 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
- soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels
- 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
- parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature
- deposits are largely in parenchyma and in diffuse form in cortex
- cerebral amyloid angiopathy (MGI Ref ID J:89848)
- 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
- 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
- microvascular amyloid beta accumulations are mainly fibrillar
- 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
- evidence of microhemorrhage is observed in microvessels with amyloid beta deposits
- microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions
- cardiovascular system phenotype
- abnormal blood circulation (MGI Ref ID 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
This mouse can be used to support research in many areas including:
APP relatedNeurobiology Research
Alzheimer's Disease
strains expressing mutant APP
Mouse/Human Gene Homologs
Alzheimer's
Neurobiology Research
Alzheimer's Disease
Neurodegeneration
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Thy1-APPSwDutIowa)BWevn | ||
|---|---|---|---|
| Allele Name | transgene insertion B, William E Van Nostrand | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | APPSwDI; Tg-SwDI; Tg-SwDI/B; | ||
| Mutation Made By | William Van Nostrand, Stony Brook University | ||
| Strain of Origin | C57BL/6 | ||
| Expressed Gene | APP, amyloid beta (A4) precursor protein, human | ||
| Promoter | Thy1, thymus cell antigen 1, theta, mouse, laboratory | ||
| Molecular Note | 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. [MGI Ref ID J:89848] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(APP), Separated QPCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Davis J; Xu F; Deane R; Romanov G; Previti ML; Zeigler K; Zlokovic BV; Van Nostrand WE. 2004. 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 279(19):20296-306. [PubMed: 14985348] [MGI Ref ID J:89848]
Additional References
Tg(Thy1-APPSwDutIowa)BWevn relatedBurgess BL; McIsaac SA; Naus KE; Chan JY; Tansley GH; Yang J; Miao F; Ross CJ; van Eck M; Hayden MR; van Nostrand W; St George-Hyslop P; Westaway D; Wellington CL. 2006. Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer's disease mouse models with abundant A beta in plasma. Neurobiol Dis 24(1):114-27. [PubMed: 16899370] [MGI Ref ID J:113199]
Carrasco J; Adlard P; Cotman C; Quintana A; Penkowa M; Xu F; Van Nostrand WE; Hidalgo J. 2006. Metallothionein-I and -III expression in animal models of Alzheimer disease. Neuroscience 143(4):911-22. [PubMed: 17027170] [MGI Ref ID J:117948]
Chow N; Bell RD; Deane R; Streb JW; Chen J; Brooks A; Van Nostrand W; Miano JM; Zlokovic BV. 2007. Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype. Proc Natl Acad Sci U S A 104(3):823-8. [PubMed: 17215356] [MGI Ref ID J:119251]
Colton CA; Wilcock DM; Wink DA; Davis J; Van Nostrand WE; Vitek MP. 2008. The effects of NOS2 gene deletion on mice expressing mutated human AbetaPP. J Alzheimers Dis 15(4):571-87. [PubMed: 19096157] [MGI Ref ID J:143551]
Davis J; Xu F; Miao J; Previti ML; Romanov G; Ziegler K; Van Nostrand WE. 2006. Deficient cerebral clearance of vasculotropic mutant Dutch/Iowa Double Ass in human AssPP transgenic mice. Neurobiol Aging 27(7):946-54. [PubMed: 16105708] [MGI Ref ID J:108851]
Fan R; Defilippis K; Van Nostrand WE. 2007. Induction of complement proteins in a mouse model of cerebral microvascular Abeta deposition. J Neuroinflammation 4(1):22. [PubMed: 17877807] [MGI Ref ID J:124911]
Hirsch-Reinshagen V; Maia LF; Burgess BL; Blain JF; Naus KE; McIsaac SA; Parkinson PF; Chan JY; Tansley GH; Hayden MR; Poirier J; Van Nostrand W; Wellington CL. 2005. The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. J Biol Chem 280(52):43243-56. [PubMed: 16207707] [MGI Ref ID J:105900]
Hutchinson D; Ho V; Dodd M; Dawson HN; Zumwalt AC; Schmitt D; Colton CA. 2007. Quantitative measurement of postural sway in mouse models of human neurodegenerative disease. Neuroscience 148(4):825-32. [PubMed: 17764851] [MGI Ref ID J:128390]
Miao J; Vitek MP; Xu F; Previti ML; Davis J; Van Nostrand WE. 2005. Reducing cerebral microvascular amyloid-beta protein deposition diminishes regional neuroinflammation in vasculotropic mutant amyloid precursor protein transgenic mice. J Neurosci 25(27):6271-7. [PubMed: 16000616] [MGI Ref ID J:99430]
Miao J; Xu F; Davis J; Otte-Holler I; Verbeek MM; Van Nostrand WE. 2005. Cerebral Microvascular Amyloid {beta} Protein Deposition Induces Vascular Degeneration and Neuroinflammation in Transgenic Mice Expressing Human Vasculotropic Mutant Amyloid {beta} Precursor Protein. Am J Pathol 167(2):505-15. [PubMed: 16049335] [MGI Ref ID J:99946]
Van Vickle GD; Esh CL; Daugs ID; Kokjohn TA; Kalback WM; Patton RL; Luehrs DC; Walker DG; Lue LF; Beach TG; Davis J; Van Nostrand WE; Castano EM; Roher AE. 2008. Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy. Am J Pathol 173(2):483-93. [PubMed: 18599612] [MGI Ref ID J:137886]
Wilcock DM; Gharkholonarehe N; Van Nostrand WE; Davis J; Vitek MP; Colton CA. 2009. Amyloid reduction by amyloid-beta vaccination also reduces mouse tau pathology and protects from neuron loss in two mouse models of Alzheimer's disease. J Neurosci 29(25):7957-65. [PubMed: 19553436] [MGI Ref ID J:150418]
Wilcock DM; Lewis MR; Van Nostrand WE; Davis J; Previti ML; Gharkholonarehe N; Vitek MP; Colton CA. 2008. Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2. J Neurosci 28(7):1537-45. [PubMed: 18272675] [MGI Ref ID J:132221]
Wilcock DM; Vitek MP; Colton CA. 2009. Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. Neuroscience 159(3):1055-69. [PubMed: 19356689] [MGI Ref ID J:148938]
Xu F; Grande AM; Robinson JK; Previti ML; Vasek M; Davis J; Van Nostrand WE. 2007. Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid beta-protein precursor transgenic mice. Neuroscience 146(1):98-107. [PubMed: 17331655] [MGI Ref ID J:122063]
Xu F; Vitek MP; Colton CA; Previti ML; Gharkholonarehe N; Davis J; Van Nostrand WE. 2008. Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice. J Neurosci 28(20):5312-20. [PubMed: 18480287] [MGI Ref ID J:136318]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice may be bred as homozygotes. Mating System Homozygote x Homozygote (Female x Male) 10-MAR-09 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $209.90 Female or Male Homozygous for Tg(Thy1-APPSwDutIowa)BWevn
Pairs /Price (US dollars $) Pair Genotype $419.80 Homozygous for Tg(Thy1-APPSwDutIowa)BWevn x Homozygous for Tg(Thy1-APPSwDutIowa)BWevn
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $272.90 Female or Male Homozygous for Tg(Thy1-APPSwDutIowa)BWevn
Pairs /Price (US dollars $) Pair Genotype $545.80 Homozygous for Tg(Thy1-APPSwDutIowa)BWevn x Homozygous for Tg(Thy1-APPSwDutIowa)BWevn
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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