Overview

Also Known As:htau

Mice that are homozygous for the targeted allele and hemizygous for the transgene express all six isoforms (including both 3R and 4R forms) of human microtubule-associated protein tau (MAPT). These mutant mice may be useful in studies examining the relationship between human MAPT and Alzheimer's disease pathogenesis

Donating Investigator

Karen Duff, Nathan Kline Institute

Peter Davies, Albert Einstein College of Medicine

Genetic overview

Genetic Background	Generation
	N9+N2F15 (2019-06-13 00:00:00)

Tg(MAPT)8cPdav

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

Mapt^tm1(EGFP)Klt

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Mapt	microtubule-associated protein tau

View Genetics

Research Applications

Neurobiology Research
Research Tools

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female 5-week

510.00 Domestic price for breeder pair

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Details

Detailed 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 pathogenesis. The Donating Investigator reports that mice homozygous for the transgenic insert have never been observed and that such mice are presumed to be embryonic lethal.

In 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.

Expression Data

Expressed Gene	MAPT, microtubule associated protein tau, human
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	GFP, Green Fluorescent Protein,
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.

Control Suggestions

Approximate Controls

Depending upon the experiment, the following may be appropriate control(s):
--Stock No. 005491 mice from the colony that are homozygous for the tauGFP targeted mutation and noncarrier for the transgene
--C57BL/6-congenic tauGFP mice (Stock No. 029219)
--C57BL/6J inbred mice (Stock No. 000664)

Additional Information

Considerations for Choosing Controls

Selected References

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):582-90PubMed: 12859672 MGI: J:84638

View All References

Genetics

Tg(MAPT)8cPdav

Allele Symbol: Tg(MAPT)8cPdav

Allele Name	transgene insertion 8c, Peter Davies
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	Tg(MAPT)8cPdav; transgene insertion 8c, Peter Davies
Gene Symbol and Name	Tg(MAPT)8cPdav, transgene insertion 8c, Peter Davies
Gene Synonym(s)	8c
Promoter	MAPT, microtubule associated protein tau, human
Expressed Gene	MAPT, microtubule associated protein tau, human
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.
Strain of Origin	Swiss Webster x (C57BL/6 x DBA)F1
Chromosome	UN
General Note	Mice that are homozygous for the Mapt^tm1(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 2 months of age.
Molecular Note	The transgene contains the coding sequence, intronic regions, and regulatory elements of the human microtubule-associated protein tau (MAPT) gene.
Mutations Made By	Peter Davies, Albert Einstein College of Medicine

Mapt^tm1(EGFP)Klt

Allele Symbol: Mapt^tm1(EGFP)Klt

Allele Name	targeted mutation 1, Kerry Lee Tucker
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Kerry Lee Tucker; Mapt^tm1(EGFP)Klt
Gene Symbol and Name	Mapt, microtubule-associated protein tau
Gene Synonym(s)	RNPTAU; MSTD; FTDP-17; Mtapt; pTau; Mtapt; MTBT1; AI413597; PPND; PPP1R103; DDPAC; Tau; expressed sequence AI413597; MTBT2; expressed sequence AW045860; MAPTL; TAU; AW045860; Tau
Expressed Gene	GFP, Green Fluorescent Protein,
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.
Strain of Origin	129S4/SvJae
Chromosome	11
Molecular Note	Exon 1 was disrupted by the insertion of a cassette encoding the EGFP fluorescent marker gene and a neomycin resistance gene. Fusion protein including EGFP 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.
Mutations Made By	Dr. Kerry Tucker, Ruprecht Karls University of Heidelberg

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Alzheimer's disease

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Mapt^tm1(EGFP)Klt related

Neurobiology Research
- Alzheimer's Disease
  - Tau (Mapt) mutants

Genotype: Tg(MAPT)8cPdav related

Neurobiology Research
- Alzheimer's Disease
  - Tau (Mapt) mutants

Neurobiology Research
- Alzheimer's Disease
Research Tools
- Fluorescent Proteins
- Genetics Research
  - Tissue/Cell Markers: neurons
  - Tissue/Cell Markers
- Neurobiology Research
  - cell marker

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/?
involves: 129S4/SvJae * C57BL/6 * Swiss Webster

hematopoietic system phenotype

abnormal spleen B cell follicle morphology
- splenic white pulp contains follicles that are larger and more irregular in shape than normal follicles and are often fused with adjacent follicles

abnormal spleen red pulp morphology
- splenic red pulp is largely obliterated

neoplasm

increased follicular lymphoma incidence
- splenic architecture is replaced by proliferated immature mononuclear cells arranged in follicular aggregates indicating follicular lymphoma

increased lymphoma incidence
- malignant lymphoma in the spleen and lymph nodes are seen in some mutants
- megakaryocytes are numerous is some spleens, suggesting a relation to megakaryocytic leukemia

nervous system phenotype

abnormal neuron morphology
- cells in the cortex and hippocampus appear irregularly shaped, often with distorted processes in 13 month old mice

tau protein deposits
- 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
- 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
- phosphorylated tau accumulates in neuronal cell bodies and dendrites of the hippocampus and neocortex as early as 3 months of age
- tau aggregates in the proximal dendrites have an average width of 15 nm and are not densely packed

renal/urinary system phenotype

abnormal renal glomerulus morphology
- kidney glomeruli are dilated probably due to obstruction from the amyloid in the lumen or walls of medullary tubules especially in the papilla

homeostasis/metabolism phenotype

amyloidosis
- amyloid deposits in the heart are not composed of amyloid-beta peptide, but rather amyloid A
- amyloid is deposited concentrically in the perifollicular sheath, partly or completely encircling the follicles in the spleen
- in the kidney, amyloid deposits are seen in the glomeruli
- in the liver, amyloid deposit is in the walls of sinusoids or central veins
- some mutants older than 18 months exhibit amyloid deposits in the spleen, kidneys, liver, ovary and/or heart

immune system phenotype

abnormal spleen B cell follicle morphology
- splenic white pulp contains follicles that are larger and more irregular in shape than normal follicles and are often fused with adjacent follicles

abnormal spleen red pulp morphology
- splenic red pulp is largely obliterated

The following phenotype relates to a compound genotype created using this strain

Genotype: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/0
B6.Cg-Mapt Tg(MAPT)8cPdav/J

behavior/neurological phenotype

abnormal spatial learning
- 6 month old mutants exhibit slower visuospatial learning than control mice
- however, mutants perform better than Tg(APPswe,PSEN1dE9)85Dbo mice on the visuospatial re-learning test at 9 and 18 months of age
- in the visuospatial re-learning test performed at 7, 8, 9, and 15 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls

mammalian phenotype

taste/olfaction phenotype
- Normal - mutants do not exhibit Alzheimer's disease-related impairment in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure

nervous system phenotype

neurofibrillary tangles

References

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):582-90PubMed: 12859672 MGI: J:84638

Additional References

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):10741-9PubMed: 19710325 MGI: J:152310
Ma QL; Zuo X; Yang F; Ubeda OJ; Gant DJ; Alaverdyan M; Teng E; Hu S; Chen PP; Maiti P; Teter B; Cole GM; Frautschy SA. 2013. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. J Biol Chem 288(6):4056-65PubMed: 23264626 MGI: J:195654
Komuro Y; Xu G; Bhaskar K; Lamb BT. 2015. Human tau expression reduces adult neurogenesis in a mouse model of tauopathy. Neurobiol Aging 36(6):2034-42PubMed: 25863528 MGI: J:222621
Dengler-Crish CM; Ball HC; Lin L; Novak KM; Cooper LN. 2018. Evidence of Wnt/beta-catenin alterations in brain and bone of a tauopathy mouse model of Alzheimer's disease. Neurobiol Aging 67:148-158PubMed: 29660685 MGI: J:264770
Wang ZH; Liu P; Liu X; Yu SP; Wang JZ; Ye K. 2018. Delta-secretase (AEP) mediates tau-splicing imbalance and accelerates cognitive decline in tauopathies. J Exp Med 215(12):3038-3056PubMed: 30373880 MGI: J:269026
Ferguson SA; Mouzon BC; Lynch C; Lungmus C; Morin A; Crynen G; Carper B; Bieler G; Mufson EJ; Stewart W; Mullan M; Crawford F. 2017. Negative Impact of Female Sex on Outcomes from Repetitive Mild Traumatic Brain Injury in hTau Mice Is Age Dependent: A Chronic Effects of Neurotrauma Consortium Study. Front Aging Neurosci 9:416PubMed: 29311903 MGI: J:275711
Rodriguez L; Mdzomba JB; Joly S; Boudreau-Laprise M; Planel E; Pernet V. 2018. Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons. Front Mol Neurosci 11:293PubMed: 30197586 MGI: J:281373
Ryan B; Williams JM; Curtis MA. 2019. Plasma MicroRNAs Are Altered Early and Consistently in a Mouse Model of Tauopathy. Neuroscience 411:164-176PubMed: 31152932 MGI: J:282885

Additional - Mapt^tm1(EGFP)Klt related

Additional - Tg(MAPT)8cPdav related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Mapt Alternate 1
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

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. The Donating Investigator reports that mice homozygous for the transgenic insert have never been observed and that such mice are presumed to be embryonic lethal.
- Additional Breeding and Husbandry Support
Mating System
- Homozygous for Mapt^tm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPdav x Homozygous for Mapt^tm1(EGFP)Klt, Noncarrier
  or
  Homozygous for Mapt^tm1(EGFP)Klt, Noncarrier x Homozygous for Mapt^tm1(EGFP)Klt, Hemizygous for Tg(MAPT)8cPda
Citation
When using the htau mouse strain in a publication, please cite the originating article(s) and include JAX stock #005491 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

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Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

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Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Mapt<tm1(EGFP)Klt>, Hemizygous or Non carrier for Tg(MAPT)8cPdav

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Mapt<tm1(EGFP)Klt> Tg(MAPT)8cPdav/J	$2595.00
Frozen Mouse Embryo	B6.Cg-Mapt<tm1(EGFP)Klt> Tg(MAPT)8cPdav/J	$2595.00
Frozen Mouse Embryo	B6.Cg-Mapt<tm1(EGFP)Klt> Tg(MAPT)8cPdav/J	$3373.50
Frozen Mouse Embryo	B6.Cg-Mapt<tm1(EGFP)Klt> Tg(MAPT)8cPdav/J	$3373.50

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Also Known As:htau

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(MAPT)8cPdav

Allele Symbol: Tg(MAPT)8cPdav

Mapttm1(EGFP)Klt

Allele Symbol: Mapttm1(EGFP)Klt

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Mapttm1(EGFP)Klt related

Genotype: Tg(MAPT)8cPdav related

Mammalian Phenotype Terms by Genotype

Genotype: Mapttm1(EGFP)Klt/Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/?involves: 129S4/SvJae * C57BL/6 * Swiss Webster

hematopoietic system phenotype

neoplasm

nervous system phenotype

renal/urinary system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Mapttm1(EGFP)Klt/Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/0B6.Cg-Mapt Tg(MAPT)8cPdav/J

behavior/neurological phenotype

mammalian phenotype

nervous system phenotype

References

Additional References

Additional - Mapttm1(EGFP)Klt related

Additional - Tg(MAPT)8cPdav related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Mapt^tm1(EGFP)Klt

Allele Symbol: Mapt^tm1(EGFP)Klt

Genotype: Mapt^tm1(EGFP)Klt related

Genotype: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/?
involves: 129S4/SvJae * C57BL/6 * Swiss Webster

Genotype: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/0
B6.Cg-Mapt Tg(MAPT)8cPdav/J

Additional - Mapt^tm1(EGFP)Klt related