B6;CBA-Tg(Camk2a-tTA)1Mmay/J

Stock number: 003010
Product name: CaMKII-tTA
Research areas: Neurobiology Research, Research Tools

Description

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].

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].

Allele

Symbol: Tg(Camk2a-tTA)1Mmay
Name: transgene insertion 1, Mark Mayford
MGI accession ID: MGI:2179066
Generation method: Transgenic
Attributes: Null/Knockout; Transactivator
Marker symbol: Tg(Camk2a-tTA)1Mmay
Marker name: transgene insertion 1, Mark Mayford
Chromosome: 12
Strain of origin: Not Specified
Expressed genes: tTA,tetracycline-controlled transactivator,E. coli
Site of expression: Expresses tTA in forebrain neurons.
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.
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.