| |||||||||||||||||||
| This strain is now distributed by the Mutant Mouse Regional Resource Center. Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for ordering information and strain details on C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
MMRRC Stock Number 034843. As a designated MMRRC center, The Jackson Laboratory will continue to distribute these mice at the same high health and quality standards but ordering is exclusively provided through the MMRRC. | |||||||||||||||||||
| 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
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/J (Changed: 11-AUG-11 ) Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse 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.A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at the MMRRC at The Jackson Laboratory. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be C57BL/6N. These data suggest the mice sent to the MMRRC at The Jackson Laboratory were on a mixed C57BL/6J ; C57BL/6N genetic background.
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
009126 B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax
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
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Alzheimer Disease; AD
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Cerebral Amyloid Angiopathy, App-Related (APP)
assigned by genotype
Tg(Thy1-APPSwDutIowa)BWevn/0
involves: C57BL/6
- nervous system phenotype
- abnormal astrocyte morphology
- astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent (MGI Ref ID J:124911)
- abnormal microglial cell physiology
- amyloid beta deposits
- 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 (MGI Ref ID J:89848)
- soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (MGI Ref ID 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 (MGI Ref ID J:89848)
- parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (MGI Ref ID J:89848)
- deposits are largely in parenchyma and in diffuse form in cortex (MGI Ref ID J:124911)
- cerebral amyloid angiopathy
- 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 (MGI Ref ID 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 (MGI Ref ID J:89848)
- microvascular amyloid beta accumulations are mainly fibrillar (MGI Ref ID 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 (MGI Ref ID J:89848)
- evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (MGI Ref ID J:89848)
- microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (MGI Ref ID J:124911)
- immune system phenotype
- abnormal microglial cell physiology
- other phenotype
- amyloidosis
- mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta (MGI Ref ID J:89848)
- amyloid beta deposits
- 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 (MGI Ref ID J:89848)
- soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (MGI Ref ID 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 (MGI Ref ID J:89848)
- parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (MGI Ref ID J:89848)
- deposits are largely in parenchyma and in diffuse form in cortex (MGI Ref ID J:124911)
- cerebral amyloid angiopathy
- 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 (MGI Ref ID 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 (MGI Ref ID J:89848)
- microvascular amyloid beta accumulations are mainly fibrillar (MGI Ref ID 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 (MGI Ref ID J:89848)
- evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (MGI Ref ID J:89848)
- microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (MGI Ref ID J:124911)
- cardiovascular system phenotype
- abnormal blood circulation
- reduced cerebral blood flow, CBF, response (21% increase) to whisker stimulation is observed relative to controls (38% increase) at 9 months (MGI Ref ID J:119251)
- 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 (MGI Ref ID J:119251)
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 provided by MGI
| 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
Generic Tg(APP), Standard PCR
Tg(APP), Separated QPCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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]
Liao MC; Van Nostrand WE. 2010. Degradation of soluble and fibrillar amyloid beta-protein by matrix metalloproteinase (MT1-MMP) in vitro. Biochemistry 49(6):1127-36. [PubMed: 20050683] [MGI Ref ID J:159886]
Medeiros R; Kitazawa M; Caccamo A; Baglietto-Vargas D; Estrada-Hernandez T; Cribbs DH; Fisher A; Laferla FM. 2011. Loss of muscarinic m(1) receptor exacerbates Alzheimer's disease-like pathology and cognitive decline. Am J Pathol 179(2):980-91. [PubMed: 21704011] [MGI Ref ID J:174403]
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]
Ridnour LA; Dhanapal S; Hoos M; Wilson J; Lee J; Cheng RY; Brueggemann EE; Hines HB; Wilcock DM; Vitek MP; Wink DA; Colton CA. 2012. Nitric oxide-mediated regulation of beta-amyloid clearance via alterations of MMP-9/TIMP-1. J Neurochem 123(5):736-49. [PubMed: 23016931] [MGI Ref ID J:190735]
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]
Zeng Y; Callaghan D; Xiong H; Yang Z; Huang P; Zhang W. 2012. Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg-SwDI transgenic mice. J Neurochem :. [PubMed: 22578166] [MGI Ref ID J:186567]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice may be bred as homozygotes.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
This strain is currently Transferred.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Payment Terms and Conditions
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
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 Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.
Contact information
General inquiries regarding Terms of UseContracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
No Liability
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.