B6(Cg)-Tg(TPO-cre/ERT2)1139Tyj/J

Stock number: 026512
Product name: TPO-CreER
Research areas: Internal/Organ Research, Research Tools

Description

TPOCreER transgenic mice express Cre-ER^T2 under the direction of the human thyroid peroxidase promoter. They are useful for applications requiring tamoxifen-induced deletion of floxed sequences in the thyroid.

Detailed description

Expression of creER^T2 in TPOCreER transgenic mice is directed by the human thyroid peroxidase (TPO) promoter in the thyroid. TPO encodes an enzyme essential for thyroid gland function. Restricted to the cytoplasm, Cre-ER^T2 can only gain access to the nuclear compartment after exposure to tamoxifen. Homozygotes are viable and fertile. 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 B6.129P2(Cg)-Braf^tm1Mmcm/J mice (Stock No. 017837), which express the V600E mutant Braf allele after cre recombination, resulting TB offspring develop papillary thyroid carcinomas (PTCs) in a tamoxifen-dependent manner. These mice, however, lack extrathyroidal invasion and cervical lymph node metastases.

When TB mice are further crossed to B6.129S4-Trp53^tm3.1Tyj/J mice (Stock No. 008182), which express the R270H missense mutant Trp53 allele, resulting offspring displayed accelerated and aggressive PTCs and had decreased survival time after tamoxifen induction.

Development

A transgenic vector was generated including the human thyroid peroxidase (TPO) promoter driving expression of a creER^T2 fusion gene (a Cre recombinase fused to a human estrogen receptor ligand binding domain). This transgene was microinjected into fertilized C57BL/6NTac oocytes. Offspring from founder line 1139 have been maintained on a C57BL/6J background after crosses to numerous floxed alleles on congenic C57BL/6J backgrounds. The donating investigator reports that the contaminating alleles have been removed from this TPOCreER transgenic line. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Allele

Symbol: Tg(TPO-cre/ERT2)1139Tyj
Name: transgene insertion 1139, Tyler Jacks
MGI accession ID: MGI:5565332
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Marker symbol: Tg(TPO-cre/ERT2)1139Tyj
Marker name: transgene insertion 1139, Tyler Jacks
Chromosome: UN
Strain of origin: C57BL/6NTac
Expressed genes: cre/ERT2,Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of expression: Cre-ERT2 fusion protein is expressed under direction of the human TPO promoter in the thyroid.
Molecular note: A construct with the human thyroid peroxidase promoter (TPO) and an inducible cre/estrogen receptor ligand-binding domain fusion (cre/ERT2) was used to generate transgenic founders. Two founders were obtained and one (#1139) was used for further analyses.