B6.Cg-E2f1^{Tg(Wnt1-cre)2Sor}/J

Stock number: 022501
Product name: B6 Wnt1-Cre2
Research areas: Cancer Research, Neurobiology Research, Research Tools

Description

Wnt1-Cre2 transgenic mice express Cre recombinase under the control of the mouse Wnt1, wingless-related MMTV integration site 1, promoter and enhancer, and have applications in studies of cell lineage tracing in the developing neural crest and midbrain. See Detailed Description for information on germline expression.

Detailed description

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the B6 Wnt1-Cre2 mouse line (Stock No. 022501). It should be noted that the phenotype could vary from that originally described for the 129S4 Wnt1-Cre2 mouse line (Stock No. 022137). We will modify the strain description if necessary as published results become available.

Wnt1-Cre2 transgenic mice express Cre recombinase under the control of the mouse Wnt1, wingless-related MMTV integration site 1, promoter and enhancer. The transgene integrated into chromosome 2 causing a 257 bp deletion and a 45 Kb inverted segment in exon 5 of the E2f1 (E2F transcription factor 1) gene. The inversion contains all of exon 5, but deletes 23 Kb including exons 6 and 7. The deletion results in a functional knock-out of E2f1 in homozygous mice. Founder line 20 has a copy number of greater than 1-3. Cre recombinase activity is detected in both the cardiac and cranial neural crest, specifically in the branchial arches and cardiac outflow tract. When Wnt1-Cre2 transgenic mice are bred to mice containing loxP site-flanked sequences, Cre-mediated recombination results in deletion of the floxed sequences in the midbrain and developing neural tube of the resulting offspring.
Wnt1-Cre2 transgenic mice do not exhibit the ectopic transgene expression or midbrain enlargement reported for Tg(Wnt1-cre)11Rth mice (Stock Nos. 003829 / 009107) in Lewis et al. 2013 Dev Biol 379:229. However, germline expression may be observed (described below).

In 2015, the donating investigator's laboratory reported Wnt1-Cre2 on the 129S4 genetic background exhibited Cre recombinase activity in the germline. In 2022, the donating investigator further characterized their findings that 129S4 Wnt1-Cre2 mice exhibit Cre recombinase activity in male germline and spermatogonia, but not in female germline [Dinsmore et al. 2022 Genesis].
Specifically, when 129S4 Wnt1-Cre2;ROSA26^mTmG double mutant males were bred with wildtype females, 100% germline recombination was observed in ROSA26^mTmG offspring, even when Wnt1-Cre2 was not co-inherited (25/25 Cre negative embryos and 28/28 Cre positive embryos). Notably, this study found the expected pattern of recombination with no germline Cre activity in the embryos/offspring from 129S4 Wnt1-Cre2;ROSA26^mTmG double mutant females bred to wildtype males, as well as in the embryos/offspring from 129S4 ROSA26^mTmG single mutant females bred to 129S4 Wnt1-Cre2 single mutant males. As such, for Cre-lox experiments and to avoid/minimize germline deletion of floxed allele(s), researchers may consider breeding 129S4 Wnt1-Cre2 single mutant mice to floxed mice, or breed 129S4 Wnt1-Cre2;floxed double mutant females but not double mutant males. Figure 4 of their publication also provides strategies that researchers may find helpful.
Of note, it is not specifically determined if germline Cre recombinase activity is observed for Wnt1-Cre2 on the C57BL/6J genetic background (Stock No. 022501).

If the recombinase activity pattern of this allele is further characterized by the Genetic Resource Science group at The Jackson Laboratory, such findings will be reported on the Mouse Genome Informatics (MGI) Allele Detail entry (E2f1^{Tg(Wnt1-cre)2Sor}). This same information may also be found searching the MGI Recombinase Activity and MGI Gene Expression + Recombinase Activity Comparison Matrix.

Development

A transgenic insert designed by Dr. Jeffrey Bush (while at Mount Sinai School of Medicine) containing Cre recombinase, under the control of the 1.3 kb 5' promoter and 5.5 kb 3' enhancer of the mouse Wnt1, wingless-related MMTV integration site 1 was injected into fertilized 129S4 mouse eggs. Founder line 2 was subsequently established. The transgene integrated into chromosome 2 causing a 257 bp deletion and a 45 Kb inverted segment in exon 5 of the E2f1 (E2F transcription factor 1) gene. The inversion contains all of exon 5, but deletes 23 Kb including exons 6 and 7. Founder line 20 has a copy number of greater than 1-3. The mice were then backcrossed to 129S4 for 4 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S4/SvJaeJ (Stock No. 009104) at least once, and then backcrossed to C57BL/6J (Stock No. 000664) for 5 generations using a marker assisted protocol.

Allele

Symbol: E2f1^{Tg(Wnt1-cre)2Sor}
Name: transgene insertion 2, Philippe Soriano
MGI accession ID: MGI:5485027
Generation method: Transgenic
Attributes: Recombinase-expressing; Null/Knockout
Marker symbol: E2f1
Marker name: E2F transcription factor 1
Chromosome: 2
Strain of origin: C57BL/6 x C3H
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase activity is detected in both the cardiac and cranial neural crest, specifically in the branchial arches and cardiac outflow tract.
Molecular note: A transgenic insert containing cre recombinase, under the control of the 1.3 kb 5' promoter and 5.5 kb 3' enhancer of the mouse Wnt1, wingless-related MMTV integration site 1 was injected into fertilized B6C3 hybrid mouse eggs. Founder line 2 inserted into the gene at 154561346-154561603 (Build GRCm38/mm10) resulting in a 257 bp deletion and a 45 Kb inverted segment in exon 5 of the gene. The inversion contains all of exon 5, but deletes 23 Kb including exons 6 and 7. Founder line 2 has a copy number of 1-3.