Strain Name:

STOCK Tg(tetO-ABL1*P242E*P249E)CPdav/J

Stock Number:

014544

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
This transgenic mouse has a Tet response element upstream of a human c-Abl 1b isoform modified to harbor two amino acid substitutions (P242E/P249E) in the conserved proline residues of the SH2-SH3 linker region that render the protein constitutively active (AblPP). Expression may be contoled via the Tet-Off/Tet-On system for use in studies related to tau phosphorylation.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.Cg-Tg(tetO-ABL1*P242E*P249E)CPdav/J    (Changed: 24-JAN-12 )
Type Mutant Stock; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationN8pN1
Generation Definitions
 
Donating Investigator Peter Davies,   Albert Einstein College of Medicine

Description
Hemizygous AblPP transgenic mice are viable and fertile with no reported phenotypic abnormalities. The TRE-AblPP transgene has the Tet response element (TRE or tetO) upstream of a human c-Abl 1b isoform modified to harbor two amino acid substitutions (P242E/P249E) in the conserved proline residues of the SH2-SH3 linker region that render the protein constitutively active (AblPP). When bred with other mice expressing tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), AblPP expression in the resulting double mutant offspring can be regulated with tetracycline or its analog doxycycline (dox). As designed, AblPP transgenic mice have no reported levels of AblPP expression in the absence of tTA.

These AblPP transgenic mice allow Tet-Off/Tet-On expression of a constitutively active form of c-Abl, and may be may be useful for studying tau phosphorylation and the pathogenesis of neurodegeneration/neuroinflammation associated with Alzheimer's disease. For example, when bred to a strain expressing tTA in forebrain neurons (Stock No. 007004), the resulting AblPP/tTA double mutant mice develop early reactive gliosis and astrocyctosis that continues to a severe, progressive neurodegeneration in the CA1 region of the hippocampus. Such double mutant mice will be available as Stock No. 015838.

Development
The TRE-AblPP transgene was designed with a Tet response element (TRE) followed by a constitutively active c-Abl sequence (AblPP) and a beta-globin polyA sequence. The Tet response element (TRE) contains seven copies of the 42-bp tet operator sequence (tetO) just upstream of a minimal CMV promoter. To generate the AblPP sequence, a cDNA sequence encoding the nuclear-localizing isoform (1b) of the human c-Abl (ABL1; c-abl oncogene 1, non-receptor tyrosine kinase) was modified via site-directed mutagenesis to change the conserved proline residues of the SH2-SH3 linker region to glutamate (P242E/P249E). The 5.4 kb TRE-AblPP transgene was injected into the embryos of FVB/NTac mice. Founder mice were bred with FVB/NTac mice to establish founder line C. The colony was then maintained for several generations by breeding TRE-AblPP females with CaMKIIa-tTA males (on a C57BL/6 genetic background; see Stock No. 007004). During this time, two generations of backcrossing TRE-AblPP males with C57BL/6J females are also reported. TRE-AblPP transgenic mice (not harboring the Camk2a-tTA transgene) on a mixed C57BL/6J;FVB/N genetic background were sent to The Jackson Laboratory Repository (see SNP note below). Upon arrival, TRE-AblPP transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 27 SNP (single nucleotide polymorphism) panel analysis covering all 19 chromosomes and the X chromosome was performed on the rederived living colony at The Jackson Laboratory Repository. 13 of 27 markers (representing 12 different chromosomes) were found to be segregating for allele-type other than C57BL/6. Ten of these 13 markers had the allele-type shared by FVB/NJ and CBA/J. The other three markers (one each on chromosomes 5, 11, and 16) were neither C57BL/6J nor FVB/NJ allele-type, and had the allele-type shared by CBA/J. Taken with the strain development history, these data suggest the mice sent to The Jackson Laboratory Repository are a mix of C57BL/6 and FVB/N, with some remaining CBA genomic contributions left over from the CaMKIIa-tTA breedings.

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls

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Additional Web Information

Tet Expression Systems

Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Research Applications

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

Cell Biology Research
Signal Transduction

Immunology, Inflammation and Autoimmunity Research
Intracellular Signaling Molecules

Neurobiology Research
Alzheimer's Disease
      inducible models
Astrocyte Defects
      astrocytosis
Neurodegeneration
Tet Expression System
      tTA/rtTA Responsive Strains

Research Tools
Genetics Research
      Mutagenesis and Transgenesis: Tetop Tet System
Neurobiology Research
      Tetop Tet System
Tet Expression Systems
      tTA/rtTA Responsive Strains

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(tetO-ABL1*P242E*P249E)CPdav
Allele Name transgene insertion C, Peter Davies
Allele Type Transgenic (Constitutively active, Inducible, Inserted expressed sequence)
Common Name(s) AblPP; TRE-AblPP; TRE-c-AblPP; c-AblPP;
Mutation Made By Peter Davies,   Albert Einstein College of Medicine
Strain of OriginFVB/NTac
Site of ExpressionIn the absence of dox (off-dox), AblPP/tTA mice exhibit forebrain-specific neuronal expression of the constitutively active AblPP. No significant AblPP expression is observed in the cerebellum or brainstem (with or without dox). Greatly increased c-Abl kinase activity (20- to 30-fold) and increased c-Abl phosphorylation at tyrosine 412 is observed in the forebrain of AblPP/tTA mice off-dox compared to control mice. AblPP/tTA mice exhibit substantial microgliosis (beginning ~3 weeks off-dox) and astrocyctosis (beginning ~6-9 weeks off-dox).
Expressed Gene ABL1, ABL proto-oncogene 1, non-receptor tyrosine kinase, human
Promoter tetO, tet operator,
Molecular Note The TRE-AblPP transgene was designed with a Tet response element (TRE) followed by a constitutively active c-Abl sequence (AblPP) and a beta-globin polyA sequence. The Tet response element (TRE) contains seven copies of the 42-bp tet operator sequence (tetO) just upstream of a minimal CMV promoter. To generate the AblPP sequence, a cDNA sequence encoding the nuclear-localizing isoform (1b) of the human c-Abl (ABL1; c-abl oncogene 1, non-receptor tyrosine kinase) was modified via site-directed mutagenesisto change the conserved proline residues of the SH2-SH3 linker region to glutamate (P242E/P249E). [MGI Ref ID J:169520]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Generic tTA,

MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Schlatterer SD; Tremblay MA; Acker CM; Davies P. 2011. Neuronal c-Abl Overexpression Leads to Neuronal Loss and Neuroinflammation in the Mouse Forebrain. J Alzheimers Dis 25(1):119-133. [PubMed: 21368377]  [MGI Ref ID J:169520]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, transgene carrier mice may be bred together or to wildtype (noncarrier) mice from the colony. The donating investigator reports they have not tried to generate homozygous mice.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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