Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   13-AUG-08 Species laboratory mouse Generation N9+F3 (15-JAN-09)   Donating Investigator Michael Vitek,   Duke University Medical Center

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by RT-PCR analysis of total brain RNA, Western blot analysis of total brain homogenates or immunostraining of coronal brain sections. Hippocampal neurons from homozygous embryos, in primary culture, have delayed axonal extension and shorter total dendritic length when compared to wildtype controls. Mitochondria in the primary culture cells cluster at the distal end of axons. The frequency and velocity of mitochondrial anterograde movements is increased.

This mutant mouse strain may be useful in studies of neuronal development, axonogenesis, and organelle movement.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 1. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells from Genome Systems. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for at least 8 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mapt

005491	B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
004808	STOCK Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
004779	STOCK Mapttm1(EGFP)Klt/J

View Strains carrying other alleles of Mapt     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Mapt^tm1Hnd/Mapt⁺

        involves: C57BL/6

• behavior/neurological phenotype
• decreased susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
  • severity is reduced and seizure onset is delayed after pentylenetetrazole treatment compared to wild-type mice
  • mice are resistant to kainate-induced seizures over a larger range of doses than wild-type mice
• nervous system phenotype
• decreased susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
  • severity is reduced and seizure onset is delayed after pentylenetetrazole treatment compared to wild-type mice
  • mice are resistant to kainate-induced seizures over a larger range of doses than wild-type mice

Mapt^tm1Hnd/Mapt^tm1Hnd

        involves: C57BL/6

• behavior/neurological phenotype
• decreased susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
  • severity is reduced and seizure onset is delayed after pentylenetetrazole treatment compared to wild-type mice
  • mice are resistant to kainate-induced seizures over a larger range of doses than wild-type mice
• nervous system phenotype
• decreased susceptibility to pharmacologically induced seizures (MGI Ref ID J:121330)
  • severity is reduced and seizure onset is delayed after pentylenetetrazole treatment compared to wild-type mice
  • mice are resistant to kainate-induced seizures over a larger range of doses than wild-type mice

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mapt^tm1Hnd/Mapt^tm1Hnd

        involves: 129X1/SvJ * C57BL/6

• nervous system phenotype
• abnormal axon outgrowth (MGI Ref ID J:78649)
  • neuronal cultures from E16 mice show less axonal extension than wild-type neurons; mutant neurons lag behind wild-type in development over initial 2 days in culture, then catch up, but total sum of minor processes/axonal lengths is less than wild-type
• abnormal dendrite morphology (MGI Ref ID J:78649)
  • between 4 and 7 days in culture, total dendritic length of mutant neurons is less than in wild-type; after 7 days in culture, neurons still lag behind wild-type showing more developmental delay

View Research Applications

Research Applications

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

Neurobiology Research
Alzheimer's Disease

Research Tools
Neurobiology Research

Mapt^tm1Hnd related

Neurobiology Research
Alzheimer's Disease
      Tau (Mapt) mutants

Genes & Alleles

Gene & Allele Information

Allele Symbol		Mapttm1Hnd
Allele Name		targeted mutation 1, Hana N Dawson
Allele Type		Targeted (knock-out)
Common Name(s)		TAU-;
Mutation Made By		Michael Vitek,   Duke University Medical Center
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, encoding the translational start site, was replaced by a neomycin selection cassette via homologous recombination. RT-PCR analysis of total brain RNA obtained from homozygous mutant mice showed a lack of transcript produced by the targeted locus.The absence of encoded protein was verified by Western blot analysis of brain homogenates as well as by immunocytochemical analysis of coronal sections. [MGI Ref ID J:78649]

Genotyping

Genotyping Information

Genotyping Protocols

Mapt^tm1Hnd, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Dawson HN; Ferreira A; Eyster MV; Ghoshal N; Binder LI; Vitek MP. 2001. Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice. J Cell Sci 114(Pt 6):1179-87. [PubMed: 11228161]  [MGI Ref ID J:78649]

Jimenez-Mateos EM; Gonzalez-Billault C; Dawson HN; Vitek MP; Avila J. 2006. Role of MAP1B in axonal retrograde transport of mitochondria. Biochem J 397(1):53-9. [PubMed: 16536727]  [MGI Ref ID J:116415]

Additional References

Mapt^tm1Hnd related

Fuster-Matanzo A; de Barreda EG; Dawson HN; Vitek MP; Avila J; Hernandez F. 2009. Function of tau protein in adult newborn neurons. FEBS Lett 583(18):3063-8. [PubMed: 19695252]  [MGI Ref ID J:153129]

Higuchi M; Ishihara T; Zhang B; Hong M; Andreadis A; Trojanowski J; Lee VM. 2002. Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration. Neuron 35(3):433-46. [PubMed: 12165467]  [MGI Ref ID J:78400]

Meilandt WJ; Yu GQ; Chin J; Roberson ED; Palop JJ; Wu T; Scearce-Levie K; Mucke L. 2008. Enkephalin elevations contribute to neuronal and behavioral impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci 28(19):5007-17. [PubMed: 18463254]  [MGI Ref ID J:135174]

Palop JJ; Chin J; Roberson ED; Wang J; Thwin MT; Bien-Ly N; Yoo J; Ho KO; Yu GQ; Kreitzer A; Finkbeiner S; Noebels JL; Mucke L. 2007. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55(5):697-711. [PubMed: 17785178]  [MGI Ref ID J:126808]

Rapoport M; Dawson HN; Binder LI; Vitek MP; Ferreira A. 2002. Tau is essential to beta -amyloid-induced neurotoxicity. Proc Natl Acad Sci U S A 99(9):6364-9. [PubMed: 11959919]  [MGI Ref ID J:125456]

Roberson ED; Scearce-Levie K; Palop JJ; Yan F; Cheng IH; Wu T; Gerstein H; Yu GQ; Mucke L. 2007. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 316(5825):750-4. [PubMed: 17478722]  [MGI Ref ID J:121330]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   13-AUG-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

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.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

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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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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical 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

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

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