129S.Cg-Tg(Arc-cre/ERT2)MRhn/CdnyJ

Stock number: 039977
Product name: 129S.ArcCreER^T2
Research areas: Neurobiology Research, Research Tools

Description

129S.ArcCreER^T2 mice, backcrossed to 129S, express Cre-ER^T2 under the direction of the activity regulated cytoskeletal-associated protein (Arc) promoter/enhancer regions. They are useful in comparing activation of neuronal populations in the hippocampus during encoding and retrieval of memory.

Note that this transgene is also available on a C57BL/6-congenic background (Stock No. 022357).

Detailed description

Expression in this ArcCreER^T2 transgenic line, backcrossed to 129S, is directed by the activity regulated cytoskeletal-associated protein (Arc) promoter/enhancer regions on the BAC transgene. Arc is an immediate early gene (IEG) expressed in the dentate gyrus (DG) and CA3 regions of the hippocampus which is involved in synaptic plasticity, contextual memory formation, and fear conditioning. These mice express Cre-ER^T2 protein in neurons of the hippocampus. Restricted to the cytoplasm, Cre-ER^T2 gains access to the nuclear compartment after exposure to tamoxifen. Mice hemizygous for the BAC ArcCreER^T2 transgene are viable and fertile. The viability/fertility of homozygous transgenic mice has not been characterized by the donating laboratory. When these mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the cre-expressing cells of the offspring.

For example, when bred to B6.129X1-Gt(ROSA)26Sor^tm1(EYFP)Cos/J mice (Stock No. 006148) a floxed STOP-enhanced yellow fluorescent protein (EYFP) reporter strain, Cre-recombination in the offspring results in EYFP expression in the DG and CA3 regions of the hippocampus following administration of tamoxifen. In these mice the activation of the DG, as evident by EYFP expression, was higher during memory formation, while activation of CA3 neurons was higher during memory retrieval.

When bred to B6;129S-Gt(ROSA)26Sor^{tm35.1(CAG-aop3/GFP)Hze}/J mice (Stock No. 012735) a floxed STOP-Archaerhodopsin-3 (Arch)-enhanced green fluorescent protein (EGFP) reporter strain, Cre-recombination in the offspring results in Arch-EGFP fusion protein expression following administration of tamoxifen. Arch-EGFP expression leads to reversible photoinhibition of action potential firing/neural activity in DG and CA3 regions of the hippocampus. Optogenetic inhibition (light ON) by use of fiber optics implanted directly above the Arch-GFP⁺ DG or Arch-GFP⁺ CA3 inhibited retrieval of previously learned fear memory.

Note that this transgene is also available on a C57BL/6-congenic background (Stock No. 022357).

Development

Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a BAC (#RP23-429N15) containing the entire mouse activity regulated cytoskeletal-associated protein (Arc) gene. A CreER^T2 fusion gene (a Cre recombinase fused to a human estrogen receptor ligand binding domain), followed by a SV40 polyadenylation sequence, was inserted into the translation initiation site of Arc. This BAC was microinjected into fertilized C57BL/6J x CBA oocytes. Offspring from founder line M have been backcrossed to C57BL/6J mice for at least 15 generations (Stock No. 022357).

Dr. Christine Ann Denny backcrossed the C57BL/6-congenic (Stock No. 022357) transgenic mice to an 129/SvEv inbred mouse line for over 20 generations before sending mice to The Jackson Laboratory in 2025. The resulting 129S-congenic strain is called 129S.Cg-Tg(Arc-cre/ERT2)MRhn/CdnyJ (Stock No. 039977). To establish a live colony at The Jackson Laboratory, 129S.ArcCreER^T2 females and males were bred together and embryos cryopreserved.

Allele

Symbol: Tg(Arc-cre/ERT2)MRhn
Name: transgene insertion M, Rene Hen
MGI accession ID: MGI:5607252
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: ArcCreER^T2
Marker symbol: Tg(Arc-cre/ERT2)MRhn
Marker name: transgene insertion M, Rene Hen
Chromosome: UN
Strain of origin: C57BL/6J x CBA
Expressed genes: cre/ERT2,Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of expression: Hippocampus.
Molecular note: Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a BAC (#RP23-429N15) containing the entire mouse activity regulated cytoskeletal-associated protein (Arc) gene. A CreERT2 fusion gene (a Cre recombinase fused to a human estrogen receptor ligand-binding domain), followed by an SV40 polyadenylation sequence, was inserted into the translation initiation site of the gene. Founder lines M and F were established and maintained.