B6N.Cg-Commd10^{Tg(Vav1-icre)A2Kio}/J

Stock number: 018968
Product name: Vav-iCre
Research areas: Cancer Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Vav-iCre transgenic mice have the mouse HS21/45 control regions directing expression of an optimized variant of Cre recombinase (iCre) to hematopoietic cells (and their progenitors), and may be useful for generating conditional mutations in hematopoietic cells.

In Goodwin et al. 2019 Genome Res. 29:494, it was discovered that the transgene integrated into an intron of Commd10 (COMM domain containing 10) on chromosome 18 - creating a Commd10 null allele.

Detailed description

It should be noted that the phenotype of these C57BL/6NJ-congenic Vav-iCre transgenic mice (Stock No. 018968) could vary from that of the parental line originally described on a different genetic background (Stock No. 008610). We may modify the C57BL/6NJ-congenic strain description if necessary as published results become available.

Vav-iCre transgenic mice express an improved Cre recombinase (iCre) under the control of the mouse vav 1 oncogene (Vav1) promoter. The transgene integrated into an intron of Commd10 (COMM domain containing 10) on chromosome 18. The insertion results in a functional knock-out of Commd10 in homozygous mice.

Mice hemizygous for this Vav-iCre transgene are viable and fertile, with the mouse HS21/45-vav control regions directing expression of an optimized variant of Cre recombinase (iCre) to hematopoietic cells (and their progenitors). Using crosses to a reporter strain, variegated germ line (testis and ovaries), and heart and gut expression is also reported. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequence(s) in the offspring. These Vav-iCre transgenic mice may be useful for generating conditional mutations in hematopoietic cells.

Joseph et al. 2013 Cell Stem Cell 13:520 reports that Vav-iCre mice express iCre in hematopoietic cells and endothelial cells, as well as in the testes. For Cre-lox experiments and to avoid/minimize germline deletion of the floxed allele, researchers may consider breeding Vav-iCre females with floxed males. However, female germline expression may also be observed (see below).

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 (Commd10^{Tg(Vav1-icre)A2Kio}). This same information would also be found searching the MGI Recombinase Activity database.

The Vav-iCre strain allows reliable deletion of specific genes throughout the entire hematopoietic compartment, whereas the hCD2-iCre strain (Stock No. 008520) allows targeting to be focused to T cells and B cells.

To be more suitable for use with C57BL/6N-congenic Knockout Mouse Project (KOMP) strains with floxed alleles, The Jackson Laboratory Repository chose several Cre recombinase-expressing strains and backcrossed them onto the C57BL/6N genetic background using a marker-assisted, speed-congenic approach. This approach employed 148 single nucleotide polymorphism (SNP) markers that differ between the C57BL/6N and C57BL/6J substrains, covering all 19 chromosomes and the X chromosome. For Stock No. 018968, this analysis determined that the colony has at least 143/148 markers (97%) as C57BL/6N allele-type. Because 3 of the 5 segregating markers are on chromosome 18 (~15.4-72.4 Mbp), this region may represent the transgene insertion site. In 2018, it was discovered that the transgene integrated into the Commd10 locus on chromosome 18.

Development

The Vav-iCre transgene was generated in (CBA/Ca x C57BL/10)F1 fertilized oocytes and then backcrossed onto the C57BL/6J genetic background prior to arrival at The Jackson Laboratory Repository in 2009 as Stock No. 008610. In 2012, some Stock No. 008610 mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for many generations using a marker-assisted, speed congenic approach to generate this C57BL/6NJ-congenic strain as Stock No. 018968. This approach employed 148 single nucleotide polymorphism (SNP) markers that differ between the C57BL/6N and C57BL/6J substrains, covering all 19 chromosomes and the X chromosome. This analysis determined that the colony has at least 143/148 markers (97%) as C57BL/6N allele-type.
In 2018, it was discovered that the transgene integrated into an intron of Commd10 (COMM domain containing 10) on chromosome 18 - creating a Commd10 null allele.

Allele

Symbol: Commd10^{Tg(Vav1-icre)A2Kio}
Name: transgene insertion A2, Dimitris Kioussis
MGI accession ID: MGI:2449949
Generation method: Transgenic
Attributes: Recombinase-expressing; Null/Knockout
Marker symbol: Commd10
Marker name: COMM domain containing 10
Chromosome: 18
Strain of origin: (CBA/Ca x C57BL/10)F2
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase is expressed in lymph nodes, thymus, spleen, Peyer's patches, intestinal cryptopatches, ovaries and testes.
Molecular note: This transgene expresses Cre recombinase under the control of a vav promoter. This promoter was shown to be active in lymph nodes, thymus, spleen, Peyer's patches, intestinal cryptopatches, ovaries and testes. Line A2 inserted into the gene at 47022629-47022630 (Build GRCm38/mm10). The insetion results in a functional knock-out in homozygous mice.