JAX
Mouse Strain Datasheet - 003010
B6;CBA-Tg(Camk2a-tTA)1Mmay/J
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.
Donating Investigator
Dr. Mark Mayford, The Scripps Research Institute
Genetic overview
| Genetic Background | Generation |
|---|---|
|
F?+N3F2
|
Tg(Camk2a-tTA)1Mmay
| Allele Type |
|---|
| Transgenic (Transactivator) |
Detailed Description
Transgenic mice expressing the tetracycline-controlled transactivator protein (tTA) under regulatory control of the forebrain-specific calcium-calmodulin-dependent kinase II (Camk2a) promoter 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.
Expression Data
| Expressed Gene | tTA, tetracycline-controlled transactivator, E. coli |
|---|---|
| Site of Expression | Expresses tTA in forebrain neurons. |
Control Suggestions
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):1678-83. PubMed: 8939850MGI: J:37107
Tg(Camk2a-tTA)1Mmay
Allele Symbol: Tg(Camk2a-tTA)1Mmay
| Allele Name | transgene insertion 1, Mark Mayford |
|---|---|
| Allele Type | Transgenic (Transactivator) |
| Allele Synonym(s) | CAMK-rTA; CaMKII-tTA; CaMKIIalpha-tTA; CamDAT; Tg(CaMKIItTA)Mmay; Tgalpha-CaMkII-tTA; line B; pCaMKII-tTA |
| Gene Symbol and Name | Tg(Camk2a-tTA)1Mmay, transgene insertion 1, Mark Mayford |
| Gene Synonym(s) | CAMK-rTA; CaMKIIalpha-tTA; CamDAT; Tg(alphacre); Tg(CaMKIItTA)Mmay; Tgalpha-CaMkII-tTA; pCaMKII-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 | UN |
| 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. |
| Mutations Made By | Dr. Mark Mayford, The Scripps Research Institute |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Neurobiology Research
- Tet Expression System
- tTA/rtTA Expressing Strains
- Tet Expression System
- Research Tools
- Neurobiology Research
- Tetop Tet System
- Tet Expression Systems
- tTA/rtTA Expressing Strains
- Neurobiology Research
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
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 (MGI Ref ID J:185792)
- 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 (MGI Ref ID J:185792)
- Background Sensitivity - width of granule cell layer is 42% thinner than controls by 2-4 months (MGI Ref ID J:185792)
- Background Sensitivity - width of granule cell layer is 68% thinner than controls by 6-9 months (MGI Ref ID J:185792)
- however, when mice are reared on doxycycline, cell loss is not observed (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- neuronal degeneration is progressive (MGI Ref ID J:185792)
Genotype: Tg(Camk2a-tTA)1Mmay/0
(B6.Cg-Tg(Camk2a-tTA)1Mmay x FVB/NJ)F1
nervous system phenotype
- abnormal dentate gyrus morphology
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 (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 14% thinner than controls and the C57BL/6 congenic background (MGI Ref ID J:185792)
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 (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 17% thinner than controls and the C57BL/6 congenic background (MGI Ref ID J:185792)
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 (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 29% thinner than controls and C57BL/6 congenic background (MGI Ref ID J:185792)
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 (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 30% thinner than controls and the C57BL/6 congenic background (MGI Ref ID J:185792)
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 (MGI Ref ID J:235351)
- decreased dentate gyrus size
- (MGI Ref ID J:235351)
- thin cerebellar granule layer
- (MGI Ref ID J:235351)
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 (MGI Ref ID J:185792)
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 (MGI Ref ID J:185792)
- hippocampal neuron degeneration
- Background Sensitivity - width of granule cell layer is 27% thinner than controls and the C57BL/6 congenic background (MGI Ref ID J:185792)
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 (MGI Ref ID J:185792)
nervous system phenotype
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):1678-83. PubMed: 8939850MGI: J:37107
Additional References
- 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):248-53. PubMed: 11948670MGI: J:82535
- 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):1351-61. PubMed: 8980240MGI: J:37455
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