These Adcy6flox mutant mice possess loxP sites flanking exons 3-12 of the adenylate cyclase 6 (Adcy6) gene. This strain may be useful for studying cAMP-dependent cellular signaling.
Donald Kohan, University of Utah
These Adcy6flox mutant mice possess loxP sites flanking exons 3-12 of the adenylate cyclase 6 (Adcy6) gene. Adcy6 encodes AC6, an enzyme required for formation of cyclic adenosine monophosphate (cAMP) involved intracellular signal transduction. cAMP plays a role in the cellular functions such as the trafficking of proteins and the activation of ion channels. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-12 deleted in the cre-expressing tissues.
For example, when bred to B6.Cg-Tg(Aqp2-cre)1Dek/J mice (Stock No. 006881) expressing Cre recombinase in the collecting duct of the kidney, double mutant mice have reduced urine osmolality under normal and water deprivation conditions.
A targeting vector was designed to insert a frt-flanked neomycin resistance (neo) cassette followed by a loxP site upstream of exon 3, and a second loxP site downstream of exon 12 of the adenylate cyclase 6 (Adcy6) gene. The construct was electroporated into 129X1/SvJ-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with Flp transgenic mice to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene. The donating investigator reported the mice were backcrossed to C57BL/6J mice for ten generations (see SNP results below) prior to sending black male mice to The Jackson Laboratory Repository in 2013. Upon arrival, these males were used to cryopreserve sperm. To establish the living mouse colony, an aliquot of the frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
In 2013, 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 first generation rederived living colony at The Jackson Laboratory Repository. This revealed 5/27 markers, one each on chromosomes 6, 8, 9, 11 and 20(X), that were not fixed for C57BL/6 allele-type (e.g., still segregating for 129 allele-type markers). All animals had up to three segregating markers. In addition, 4/5 markers that determine C57BL/6J from C57BL/6N were also found to be segregating in some animals (one each on chromosomes 8, 11, 15 and 19; note that these markers are the same for C57BL/6N and 129). Taken together, these data suggest that the mice were backcrossed to C57BL/6 for fewer generations than reported prior to arrival at The Jackson Laboratory Repository, the mice are now a mix of C57BL/6 (~70-80%) and 129 (~20-30%) and the C57BL/6 substrain is not determined.
|Allele Name||targeted mutation 1.1, Donald E Kohan|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Adcy6, adenylate cyclase 6|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A targeting vector was designed to insert a frt-flanked neomycin resistance (neo) cassette followed by a loxP site upstream of exon 3, and a second loxP site downstream of exon 12 of the adenylate cyclase 6 (Adcy6) gene. Flp-mediated recombination removed the neo cassette and left exons 3 through 12 floxed.|
When maintaining a live colony, heterozygous or homozygous mice may be bred together.
When using the B6;129-Adcy6tm1.1Dek/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022503 in your Materials and Methods section.