JAX Mouse Strain Datasheet - 014544

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

Stock No:: 014544

Transgenic

Cryo Recovery

Overview

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.

Donating Investigator

Peter Davies, Albert Einstein College of Medicine

Genetic overview

Genetic Background	Generation

Tg(tetO-ABL1P242EP249E)CPdav

Allele Type
Transgenic (Constitutively active, Humanized sequence, Inducible, Inserted expressed sequence)

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Research Applications

Cell Biology Research
Immunology, Inflammation and Autoimmunity Research
Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed 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.

Expression Data

Expressed Gene	ABL1, ABL proto-oncogene 1, non-receptor tyrosine kinase, human
Site of Expression	In 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

Site of Expression

In 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).

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Schlatterer SD; Tremblay MA; Acker CM; Davies P. 2011. Neuronal c-Abl Overexpression Leads to Neuronal Loss and Neuroinflammation in the Mouse Forebrain.. In: . . MGI: J:169520

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Genetics

Tg(tetO-ABL1P242EP249E)CPdav

Allele Symbol: Tg(tetO-ABL1P242EP249E)CPdav

Allele Name	transgene insertion C, Peter Davies
Allele Type	Transgenic (Constitutively active, Humanized sequence, Inducible, Inserted expressed sequence)
Allele Synonym(s)	AblPP; TRE-AblPP; TRE-c-AblPP; c-AblPP
Gene Symbol and Name	Tg(tetO-ABL1P242EP249E)CPdav, transgene insertion C, Peter Davies
Gene Synonym(s)
Promoter	tetO, tet operator,
Expressed Gene	ABL1, ABL proto-oncogene 1, non-receptor tyrosine kinase, human
Site of Expression	In 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).
Strain of Origin	FVB/NTac
Chromosome	UN
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 mutagenesis to change the conserved proline residues of the SH2-SH3 linker region to glutamate (P242E/P249E).
Mutations Made By	Peter Davies, Albert Einstein College of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

References

Schlatterer SD; Tremblay MA; Acker CM; Davies P. 2011. Neuronal c-Abl Overexpression Leads to Neuronal Loss and Neuroinflammation in the Mouse Forebrain.. In: . . MGI: J:169520

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier forTg(tetO-ABL1P242EP249E)CPdav

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

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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.

Terms Of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(tetO-ABL1*P242E*P249E)CPdav

Allele Symbol: Tg(tetO-ABL1*P242E*P249E)CPdav

Disease Terms

Research Areas By Genotype

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

References

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

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

Tg(tetO-ABL1P242EP249E)CPdav

Allele Symbol: Tg(tetO-ABL1P242EP249E)CPdav