Overview

Also Known As: CaMKII-tTA

A C57BL/6J congenic version of this strain is available as Stock No. 007004.

When these Camk2a-tTA transgenic mice are mated to strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (TRE; tetO), expression of the target gene can be blocked by administration of the tetracycline analog, doxycycline. These mice are a "Tet-Off" tool that allow the inducible expression of genes in forebrain neurons, and may be useful in studying brain disorders such as Alzheimer's, Parkinson's disease, or other neurodegenerative diseases.

As described for Stock No. 007004, the CaMK2a-tTA transgene integrated into chromosome 12 causing a 508 Kb deletion that spans the 3' half of Vipr2, the entire Wdr60, Esyt2, D430020J02Rik and Ncapg2 loci and the first two exons of Ptprn2. Homozygous mice will therefore have a functional knock-out of the deleted loci, and altered or null expression of Vipr2 and Ptprn2. Founder line 1 has >20 transgene copies [Goodwin et al. 2019 Genome Res. 29:494].

Donating Investigator

Dr. Mark Mayford, The Scripps Research Institute

Genetic overview

Genetic Background	Generation

Tg(Camk2a-tTA)1Mmay

Allele Type
Transgenic (Null/Knockout, Transactivator)

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

CaMK2a-tTA transgenic mice express the tetracycline-controlled transactivator protein (tTA) under regulatory control of the forebrain-specific calcium-calmodulin-dependent kinase II (Camk2a) promoter.

As described for Stock No. 007004, the CaMK2a-tTA transgene integrated into chromosome 12 causing a 508.12 Kb deletion that spans the 3' half of Vipr2 (vasoactive intestinal peptide receptor 2), the entire Wdr60 (WD repeat domain 60), Esyt2 (extended synaptotagmin-like protein 2), D430020J02Rik (RIKEN cDNA D430020J02 gene) and Ncapg2 (non-SMC condensin II complex, subunit G2) loci and the first two exons of Ptprn2 (protein tyrosine phosphatase, receptor type, N polypeptide 2). Homozygous mice will therefore have a functional knock-out of the deleted loci (Wdr60, Esyt2, D430020J02Rik, Ncapg2), and altered or null expression of Vipr2 and Ptprn2. Founder line 1 has a copy number of greater than 20 [Goodwin et al. 2019 Genome Res. 29:494].

Hemizygous mice are viable and fertile. When hemizygotes are mated to a second strain carrying a gene of interest under the regulatory control of a tetracycline-responsive promoter element (TRE; tetO), expression of the target gene can be blocked by administration of the tetracycline analog, doxycycline (dox). These mice are a "Tet-Off" tool that allow the inducible expression of genes in forebrain neurons, and may be useful in studying brain disorders such as Alzheimer's disease (when used in conjunction with Stock No. 005706, Stock No. 007049, Stock No. 007051, Stock No. 007052), Parkinson's disease (Stock No. 013583), or other neurodegenerative diseases.

Of note, mice expressing Tg(Camk2a-tTA)1Mmay on the C57BL/6 background exhibit resistance to tTA-induced neurotoxicity (dentate gyrus granule cell layer atrophy). All other backgrounds tested (FVB/NJ, CBA/J, 129X1/SvJ, C3H/HeJ, DBA/1J) exhibit varying levels of neurotoxicity (Han et al. 2012 J Neurosci 32:10574).

Development

A transgenic construct was designed with 8.5 kb of the mouse CaMKIIalpha promoter placed upstream of the tetracycline-regulated transactivator (tTA or Tet-Off) gene (flanked by an artificial intron and splice sites at the 5' end and by a polyadenylation signal from SV40 at the 3' end). Founder line B was established and maintained on a mixed B6;CBA genetic background upon its arrival at The Jackson Laboratory.

As described for Stock No. 007004, the CaMK2a-tTA transgene integrated into chromosome 12 causing a 508.12 Kb deletion that spans the 3' half of Vipr2 (vasoactive intestinal peptide receptor 2), the entire Wdr60 (WD repeat domain 60), Esyt2 (extended synaptotagmin-like protein 2), D430020J02Rik (RIKEN cDNA D430020J02 gene) and Ncapg2 (non-SMC condensin II complex, subunit G2) loci and the first two exons of Ptprn2 (protein tyrosine phosphatase, receptor type, N polypeptide 2). Homozygous mice will therefore have a functional knock-out of the deleted loci (Wdr60, Esyt2, D430020J02Rik, Ncapg2), and altered or null expression of Vipr2 and Ptprn2. Founder line 1 has a copy number of greater than 20 [Goodwin et al. 2019 Genome Res. 29:494].

Expression Data

Expressed Gene	tTA, tetracycline-controlled transactivator, E. coli
Site of Expression	Expresses tTA in forebrain neurons.

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Mayford M; Bach ME; Huang YY; Wang L; Hawkins RD; Kandel ER. 1996. Control of memory formation through regulated expression of a CaMKII transgene. Science 274(5293):1678-83PubMed: 8939850 MGI: J:37107

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Genetics

Tg(Camk2a-tTA)1Mmay

Allele Symbol: Tg(Camk2a-tTA)1Mmay

Allele Name	transgene insertion 1, Mark Mayford
Allele Type	Transgenic (Null/Knockout, Transactivator)
Allele Synonym(s)	Tg(Camk2a-tTA)1Mmay; transgene insertion 1, Mark Mayford
Gene Symbol and Name	Tg(Camk2a-tTA)1Mmay, transgene insertion 1, Mark Mayford
Gene Synonym(s)	Tg^{(CaMKIItTA)Mmay}; CamDAT; Tg^{alpha-CaMkII-tTA}; Tg(alphacre); pCaMKII-tTA; CAMK-rTA; CaMKIIalpha-tTA
Promoter	Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Expressed Gene	tTA, tetracycline-controlled transactivator, E. coli
Site of Expression	Expresses tTA in forebrain neurons.
Strain of Origin	Not Specified
Chromosome	12
General Note	This transgene is line B. Transgenic mice are viable, fertile, and display no overt phenotypic defects. Administration of tetracycline analogs such as doxycycline blocks transgene expression.
Molecular Note	The transgene contains the tetracycline-controlled transactivator protein (tTA) under regulatory control of the forebrain specific calcium/calmodulin-dependent kinase II promoter. The transgene integrated into chromosome 12 causing a 508.12 Kb deletion and disrupting the following genes: Vipr2, Wdr60, Esyt2, Ncapg2, and Ptprn2. The deletion results in a functional knock-out of Vipr2, Wdr60, Esyt2, and Ncapg2 in homozygous mice. Founder line 1 has a copy number of greater than 20.
Mutations Made By	Dr. Mark Mayford, The Scripps Research Institute

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Neurobiology Research
  - Tetop Tet System
- Tet Expression Systems
  - tTA/rtTA Expressing Strains
Neurobiology Research
- Tet Expression System
  - tTA/rtTA Expressing Strains

Mammalian Phenotype Terms by Genotype

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

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1

nervous system phenotype

abnormal dentate gyrus morphology
- Background Sensitivity - width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1

nervous system phenotype

abnormal dentate gyrus morphology
- Background Sensitivity - width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1

behavior/neurological phenotype

impaired contextual conditioning behavior
- Background Sensitivity - freezing in response to unsignaled foot shock decreases in mutant and increases in control during final minutes of 5 minute test

nervous system phenotype

abnormal dentate gyrus morphology
- Background Sensitivity - width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1

nervous system phenotype

abnormal dentate gyrus morphology
- Background Sensitivity - width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1

nervous system phenotype

abnormal dentate gyrus morphology
- however, doxycycline administered in the first 6 weeks of life protects against cell loss
- Background Sensitivity - width of dentate gyrus granule cell layer is 21% thinner than controls and the C57BL/6 congenic background

hippocampal neuron degeneration
- however, doxycycline administered in the first 6 weeks of life protects against cell loss
- Background Sensitivity - width of dentate gyrus granule cell layer is 21% thinner than controls and the C57BL/6 congenic background

Genotype: Tg(Camk2a-tTA)1Mmay/?
B6.Cg-Tg(Camk2a-tTA)1Mmay

behavior/neurological phenotype

abnormal long term spatial reference memory
- mice swim less distance in the target quadrant than controls when tested for long-term recall suggesting a memory consolidation impairment

mammalian phenotype

nervous system phenotype
- Normal - granule cell layer is similar to control at all time points studied
- Background Sensitivity - no evidence of overt dentate degeneration on the C57BL/6 congenic background as compared to C3H/He and CBA genetic backgrounds

Genotype: Tg(Camk2a-tTA)1Mmay/0
involves: C3H/HeJ * C57BL/6 * CBA

nervous system phenotype

abnormal dentate gyrus morphology
- Background Sensitivity - cell loss is not observed in 2 week old mice
- Background Sensitivity - granule cell layer of the dentate gyrus is reduced and disorganized in 2 month old mice as compared to non-transgenic controls and the C57BL/6 congenic background
- however, when mice are reared on doxycycline, cell loss is not observed
- Background Sensitivity - width of granule cell layer is 42% thinner than controls by 2-4 months
- Background Sensitivity - width of granule cell layer is 68% thinner than controls by 6-9 months

hippocampal neuron degeneration
- neuronal degeneration is progressive

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ

nervous system phenotype

abnormal dentate gyrus morphology
- Background Sensitivity - width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background

hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background

Genotype: Tg(Camk2a-tTA)1Mmay/0
129S6.Cg-Tg(Camk2a-tTA)1Mmay

nervous system phenotype

abnormal forebrain morphology
- reduced forebrain weight in 2-6, 13-17, and 24-27 month old mice

decreased dentate gyrus size

thin cerebellar granule layer

References

Mayford M; Bach ME; Huang YY; Wang L; Hawkins RD; Kandel ER. 1996. Control of memory formation through regulated expression of a CaMKII transgene. Science 274(5293):1678-83PubMed: 8939850 MGI: J:37107

Additional References

Adaikkan C; Middleton SJ; Marco A; Pao PC; Mathys H; Kim DN; Gao F; Young JZ; Suk HJ; Boyden ES; McHugh TJ; Tsai LH. 2019. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron 102(5):929-943.e8PubMed: 31076275 MGI: J:276144
Rotenberg A; Mayford M; Hawkins RD; Kandel ER; Muller RU. 1996. Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus [see comments] Cell 87(7):1351-61PubMed: 8980240 MGI: J:37455
Lindeberg J; Mattsson R; Ebendal T. 2002. Timing the doxycycline yields different patterns of genomic recombination in brain neurons with a new inducible Cre transgene. J Neurosci Res 68(2):248-53PubMed: 11948670 MGI: J:82535

Additional - Tg(Camk2a-tTA)1Mmay related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Tg(tTA)
- MELT: Tg(Camk2a-tTA)1Mmay
- Genotyping resources and troubleshooting
Breeding Considerations

Expected coat color from breeding is Black, Agouti. When maintained in a live colony, these mice were bred as wildtype sib x hemizygous or reciprocal.
- Additional Breeding and Husbandry Support
Mating System
- +/+ sibling x Hemizygote
Appearance
- agouti
  Related Genotype: A/?
  
  black
  Related Genotype: a/a
Citation
When using the CaMKII-tTA mouse strain in a publication, please cite the originating article(s) and include JAX stock #003010 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(Camk2a-tTA)1Mmay

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.

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Also Known As: CaMKII-tTA

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Camk2a-tTA)1Mmay

Allele Symbol: Tg(Camk2a-tTA)1Mmay

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Camk2a-tTA)1Mmay/0(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0(B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0(B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1

behavior/neurological phenotype

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0(B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0(B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/?B6.Cg-Tg(Camk2a-tTA)1Mmay

behavior/neurological phenotype

mammalian phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0involves: C3H/HeJ * C57BL/6 * CBA

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ

nervous system phenotype

Genotype: Tg(Camk2a-tTA)1Mmay/0129S6.Cg-Tg(Camk2a-tTA)1Mmay

nervous system phenotype

References

Additional References

Additional - Tg(Camk2a-tTA)1Mmay related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x CBA/J)F1

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x 129X1/SvJ)F1

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x DBA/1J)F1

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1

Genotype: Tg(Camk2a-tTA)1Mmay/?
B6.Cg-Tg(Camk2a-tTA)1Mmay

Genotype: Tg(Camk2a-tTA)1Mmay/0
involves: C3H/HeJ * C57BL/6 * CBA

Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x C3H/HeJ)F1 x C3H/HeJ

Genotype: Tg(Camk2a-tTA)1Mmay/0
129S6.Cg-Tg(Camk2a-tTA)1Mmay