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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6.Cg-Mapttm1(GFP)Klt Tg(MAPT)8cPdav/J (Changed: 14-APR-06 ) Type Congenic; Mutant Strain; Targeted Mutation; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System See Colony Maintenance Species laboratory mouse Generation N9+1F7 (31-DEC-08) Donating Investigator Karen Duff, Nathan Kline Institute Donating Investigator Peter Davies, Albert Einstein College of Medicine Description
Mice that are homozygous for the targeted allele and hemizygous for the transgene are viable and fertile. Although no endogenous mouse MAPT is detected, all six isoforms (including both 3R and 4R forms) of human MAPT are expressed. Hyperphosphorylated MAPT is detected in cell bodies and dendrites by three months of age. Paired helical filaments of aggregated insoluble MAPT can be isolated from brain tissue as early as two months of age. These mutant mice may be useful in studies examining the relationship between human MAPT and Alzheimer's disease pathogenesisIn an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Development
Double mutant mice were generated by crossing transgenic mice (mouse line 8C) with Mapt targeted mutant mice. The targeted mutant allele was created by inserting EGFP coding sequence into the first Mapt exon, disrupting expression of the Mapt gene and producing a cytoplasmic EGFP protein fused to the first 31 MAPT amino acids (see Stock Number 004779). The transgenic allele consists of a PAC insert of 200-250 kb that includes the coding sequence, intronic regions and regulatory elements of the human MAPT gene. The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells which were subsequently injected into C57BL/6 blastocysts. The transgenic allele was generated in embryos derived from a cross between Swiss Webster females and B6D2F1 males. Mice containing both alleles were crossed to C57BL/6 mice for nine generations by the donating investigator. Upon arrival at The Jackson Laboratory, the mice were crossed once more to C57BL/6 (N10). Offspring were mated to generate mice that are homozygous at the targeted mutant allele.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Mice from the colony that are homozygous for the targeted mutation and noncarrier for the transgene should be considered for use as controls. The most appropriate control animal will depend on the nature of the experiment. | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (225 strains)
004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J 004779 STOCK Mapttm1(EGFP)Klt/J
004808 STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
007251 B6.129-Mapttm1Hnd/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
Microtubule-Associated Protein Tau; MAPT - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Mapttm1(EGFP)Klt/Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/?
involves: 129S4/SvJae * C57BL/6 * Swiss Webster
- nervous system phenotype
- abnormal neuron morphology (MGI Ref ID J:84638)
- cells in the cortex and hippocampus appear irregularly shaped, often with distorted processes in 13 month old mice
- tau protein deposits (MGI Ref ID J:84638)
- phosphorylated tau accumulates in neuronal cell bodies and dendrites of the hippocampus and neocortex as early as 3 months of age
- in particular, accumulations occur in entorhinal cortex, ventromedial hypothalamus, medial septum and the nucleus of the horizontal limb of the diagonal band
- increase in tau phosphorylation occurs at serine 202, threonine 231 and serine 235 as determined by immunoblot
- tau aggregates in the proximal dendrites have an average width of 15 nm and are not densely packed
- insoluble tau is present in both 2 and 9 month old mice
- paired helical filaments are observed in 9, 12 and 14 month old mice
This mouse can be used to support research in many areas including:
MAPT relatedNeurobiology Research
Alzheimer's Disease
Research Tools
Fluorescent Proteins
Genetics Research
Tissue/Cell Markers: neurons
Neurobiology Research
cell marker
Mapttm1(EGFP)Klt relatedNeurobiology Research
Alzheimer's Disease
Parkinson's Disease
Tg(MAPT)8cPdav relatedNeurobiology Research
Alzheimer's Disease
Tau (Mapt) mutants
Tau (Mapt) mutants
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Mapttm1(EGFP)Klt | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Kerry Lee Tucker | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | Mapttm1(GFP)Klt; tau ko; tauGFP; | ||
| Mutation Made By | Kerry Tucker, Ruprecht Karls University of Heidelberg | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/SvJae | ||
| Site of Expression | GFP signal is detected beginning a embryonic day 9 in the trigeminal ganglion and throughout the developing central nervous system by embryonic day 10.75. GFP expression persists in adults and closely resembles the expression of neuron specific beta-tubulin III. | ||
| Gene Symbol and Name | Mapt, microtubule-associated protein tau | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | AI413597; AW045860; DDPAC; FLJ31424; FTDP-17; MAPTL; MGC138549; MGC156663; MSTD; MTBT1; MTBT2; Mtapt; PPND; RNPTAU; TAU; Tau; expressed sequence AI413597; expressed sequence AW045860; pTau; | ||
| Molecular Note | Exon 1 was disrupted by the insertion of a cassette encoding EGFP and neo. Fusion protein including GFP was detected by Western blot analysis of homozygous mutant brain lysates. Fluorescent illumination indicated that expression of the reporter gene was similar to that of the endogenous gene. [MGI Ref ID J:66561] | ||
| Allele Symbol | Tg(MAPT)8cPdav | ||
| Allele Name | transgene insertion 8c, Peter Davies | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 8c; | ||
| Mutation Made By | Peter Davies, Albert Einstein College of Medicine | ||
| Strain of Origin | Swiss Webster x (C57BL/6 x DBA)F1 | ||
| Site of Expression | Neurons: EGFP signal observed at 9.0 dpc (days post-coitum) in the trilgeminal ganglion. At 10.75 dpc. EGFP was seen throughout the developing nervous system. | ||
| Expressed Gene | MAPT, microtubule-associated protein tau, human | ||
| Promoter | MAPT, microtubule-associated protein tau, human | ||
| General Note | Mice that are homozygous for the Mapttm1(GFP)Klt allele and hemizygous for the transgene are viable and fertile. Although no endogenous mouse MAPT is detected, all six isoforms (including both 3R and 4R forms) of human MAPT are expressed. Hyperphosphorylated MAPT is detected in cell bodies and dendrites by 3 months of age. Paired helical filaments of aggregated insoluble MAPT can be isolated from brain tissue as early as 2months of age. | ||
| Molecular Note | The transgene contains the coding sequence, intronic regions, and regulatory elements of the human microtubule-associated protein tau (MAPT) gene. [MGI Ref ID J:85952] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Mapttm1(EGFP)Klt, Melt Curve Analysis
Mapttm1(EGFP)Klt, Standard PCR
Tg(MAPT)8cPdav, Melt Curve Analysis
Tg(MAPT)8cPdav, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Andorfer C; Kress Y; Espinoza M; de Silva R; Tucker KL; Barde YA; Duff K; Davies P. 2003. Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J Neurochem 86(3):582-90. [PubMed: 12859672] [MGI Ref ID J:84638]
Additional References
Mapttm1(EGFP)Klt relatedTg(MAPT)8cPdav relatedAndorfer C; Acker CM; Kress Y; Hof PR; Duff K; Davies P. 2005. Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci 25(22):5446-54. [PubMed: 15930395] [MGI Ref ID J:98717]
Dickey CA; Kamal A; Lundgren K; Klosak N; Bailey RM; Dunmore J; Ash P; Shoraka S; Zlatkovic J; Eckman CB; Patterson C; Dickson DW; Nahman NS Jr; Hutton M; Burrows F; Petrucelli L. 2007. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest 117(3):648-58. [PubMed: 17304350] [MGI Ref ID J:120752]
Kelleher I; Garwood C; Hanger DP; Anderton BH; Noble W. 2007. Kinase activities increase during the development of tauopathy in htau mice. J Neurochem 103(6):2256-67. [PubMed: 17908241] [MGI Ref ID J:128741]
Korets-Smith E; Lindemann L; Tucker KL; Jiang C; Kabacs N; Belteki G; Haigh J; Gertsenstein M; Nagy A. 2004. Cre recombinase specificity defined by the tau locus. Genesis 40(3):131-8. [PubMed: 15493019] [MGI Ref ID J:94203]
Pacheco CD; Elrick MJ; Lieberman AP. 2009. Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis. Hum Mol Genet 18(5):956-65. [PubMed: 19074461] [MGI Ref ID J:145003]
Polydoro M; Acker CM; Duff K; Castillo PE; Davies P. 2009. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J Neurosci 29(34):10741-9. [PubMed: 19710325] [MGI Ref ID J:152310]
Tucker KL; Meyer M; Barde YA. 2001. Neurotrophins are required for nerve growth during development. Nat Neurosci 4(1):29-37. [PubMed: 11135642] [MGI Ref ID J:66561]
Willaredt MA; Hasenpusch-Theil K; Gardner HA; Kitanovic I; Hirschfeld-Warneken VC; Gojak CP; Gorgas K; Bradford CL; Spatz J; Wolfl S; Theil T; Tucker KL. 2008. A crucial role for primary cilia in cortical morphogenesis. J Neurosci 28(48):12887-900. [PubMed: 19036983] [MGI Ref ID J:142500]
Yuan A; Kumar A; Peterhoff C; Duff K; Nixon RA. 2008. Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice. J Neurosci 28(7):1682-7. [PubMed: 18272688] [MGI Ref ID J:132278]
Zaghetto AA; Paina S; Mantero S; Platonova N; Peretto P; Bovetti S; Puche A; Piccolo S; Merlo GR. 2007. Activation of the Wnt-beta catenin pathway in a cell population on the surface of the forebrain is essential for the establishment of olfactory axon connections. J Neurosci 27(36):9757-68. [PubMed: 17804636] [MGI Ref ID J:124891]
Andorfer C; Acker CM; Kress Y; Hof PR; Duff K; Davies P. 2005. Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci 25(22):5446-54. [PubMed: 15930395] [MGI Ref ID J:98717]
Dickey CA; Kamal A; Lundgren K; Klosak N; Bailey RM; Dunmore J; Ash P; Shoraka S; Zlatkovic J; Eckman CB; Patterson C; Dickson DW; Nahman NS Jr; Hutton M; Burrows F; Petrucelli L. 2007. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest 117(3):648-58. [PubMed: 17304350] [MGI Ref ID J:120752]
Duff K; Knight H; Refolo LM; Sanders S; Yu X; Picciano M; Malester B; Hutton M; Adamson J; Goedert M; Burki K; Davies P. 2000. Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol Dis 7(2):87-98. [PubMed: 10783293] [MGI Ref ID J:85952]
Kelleher I; Garwood C; Hanger DP; Anderton BH; Noble W. 2007. Kinase activities increase during the development of tauopathy in htau mice. J Neurochem 103(6):2256-67. [PubMed: 17908241] [MGI Ref ID J:128741]
Polydoro M; Acker CM; Duff K; Castillo PE; Davies P. 2009. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J Neurosci 29(34):10741-9. [PubMed: 19710325] [MGI Ref ID J:152310]
Tucker KL; Meyer M; Barde YA. 2001. Neurotrophins are required for nerve growth during development. Nat Neurosci 4(1):29-37. [PubMed: 11135642] [MGI Ref ID J:66561]
Yuan A; Kumar A; Peterhoff C; Duff K; Nixon RA. 2008. Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice. J Neurosci 28(7):1682-7. [PubMed: 18272688] [MGI Ref ID J:132278]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, mice that are homozygous for the targeted mutation and hemizygous for the transgene are bred with mice homozygous for the targeted mutation and wildtype for the transgene. Mating System See above 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 $236.60 Female or Male Homozygous for Mapttm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav $236.60 Female or Male Homozygous for Mapttm1(EGFP)Klt, Noncarrier
Pairs /Price (US dollars $) Pair Genotype $473.20 Homozygous for Mapttm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav x Homozygous for Mapttm1(EGFP)Klt, Noncarrier $473.20 Homozygous for Mapttm1(EGFP)Klt, Noncarrier x Homozygous for Mapttm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $307.60 Female or Male Homozygous for Mapttm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav $307.60 Female or Male Homozygous for Mapttm1(EGFP)Klt, Noncarrier
Pairs /Price (US dollars $) Pair Genotype $615.20 Homozygous for Mapttm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav x Homozygous for Mapttm1(EGFP)Klt, Noncarrier $615.20 Homozygous for Mapttm1(EGFP)Klt, Noncarrier x Homozygous for Mapttm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav
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 | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Mice from the colony that are homozygous for the targeted mutation and noncarrier for the transgene should be considered for use as controls. The most appropriate control animal will depend on the nature of the experiment. | ||
| 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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