B6.Cg-Tg(Col1a1-cre/ERT2)1Crm/J

Stock number: 016241
Research areas: Internal/Organ Research, Research Tools

Description

This Col1a1-CreERT2 mutant mouse strain carries a transgene with tamoxifen inducible Cre recombinase and may be useful for generating osteoblast and odontoblast specific targeted mutants for studies of bone physiology and homeostasis.

Detailed description

These transgenic mice express a tamoxifen inducible Cre recombinase driven by the 2.3-kb mouse Col1a1, collagen, type I, alpha 1, promoter. The transgene insert contains a fusion product involving Cre recombinase and a mutant form of the mouse estrogen receptor ligand binding domain. The mutant mouse estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the Cre/Esr1 protein can only gain access to the nuclear compartment after exposure to tamoxifen. When crossed with a strain containing a loxP site flanked sequence of interest, the offspring are useful for generating tamoxifen-induced, Cre-mediated targeted deletions. Tamoxifen administration induces Cre recombination in the osteoblasts of most bones and in odontoblasts of teeth in embryonic and postnatal mice. Inducible Cre recombinase activity is detected in the osteoblasts of the long bones of the limbs and in the ribs, vertebrae and calvaria in 18.5 embryonic day aged and 18 day old mice. Inducible Cre recombinase activity was not detected in chondrocytes. The Donating Investigator has not attempted to make this strain homozygous. Hemizygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

Of note, The Jackson Laboratory offers three mouse lines expressing tamoxifen-inducible Cre recombinase under control of the mouse Col1a1 promoter; each with unique features.
i. This Col1a1-CreERT2 transgenic mice (Stock No. 016241) has the 2.3-kb mouse Col1a1 promoter directing expression of the cre/Esr1 coding sequence; requiring only tamoxifen to induce Cre recombinase activity.
ii. Similarly, the Col1a1^{FRT-Cre-ER-T2-FRT} mice (Stock No. 027751) have a frt-flanked CreERT2 coding sequence inserted downstream of the endogenous Col1a1 promoter; requiring only tamoxifen to induce Cre recombinase activity. The additional feature is that the CreERT2 coding sequence may be removed by FLP recombinase.
iii. In contrast, the Col1a1^{FRT-STOP-FRT-Cre-ER-T2} mice (Stock No. 027750) have a frt-STOP-frt cassette and CreERT2 coding sequence, all inserted downstream of the endogenous Col1a1 promoter. As such, they require FLP recombinase-mediated removal of the frt-flanked STOP cassette prior to tamoxifen-inducible CreERT2 expression.

Development

A transgenic construct containing containing sequence encoding cre/Esr1 under the control of the 2.3-kb mouse Col1a1 (collagen, type I, alpha 1) promoter, was injected into fertilized B6D2F1/J mouse eggs. The donating investigator reported that the mice were then backcrossed to the C57BL/6 background for 5 generations(see SNP note below). Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Tg(Col1a1-cre/ERT2)1Crm
Name: transgene insertion 1, Benoit de Crombrugghe
MGI accession ID: MGI:4949435
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Marker symbol: Tg(Col1a1-cre/ERT2)1Crm
Marker name: transgene insertion 1, Benoit de Crombrugghe
Chromosome: UN
Strain of origin: (C57BL/6J x CBA/J)F1
Expressed genes: cre/ERT2,Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of expression: Inducible cre recombinase activity is detected in the osteoblasts of the long bones of the limbs and in the ribs, vertebrae and calvaria in 18.5 embryonic day aged and 18 day old mice.
Molecular note: The transgene consists of a tamoxifen-inducible cre recombinase driven by the 2.3-kb mouse Col1a1, collagen, type I, alpha 1, promoter. The transgene insert contains a fusion product involving cre recombinase and a mutant form of the mouse estrogen receptor ligand binding domain. The mutant mouse estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the cre/Esr1 protein can only gain access to the nuclear compartment after exposure to tamoxifen. Inducible cre recombinase activity is detected in the osteoblasts of the long bones of the limbs and in the ribs, vertebrae and calvaria in 18.5 embryonic day aged and 18 day old mice. Inducible cre recombinase activity was not detected in chondrocytes.