B6.FVB-Tg(Atp4b-cre)1Jig/JcmiJ

Stock number: 030656
Product name: Atp4b-Cre
Research areas: Cancer Research, Research Tools

Description

The Atp4b-Cre transgene has the parietal cell-specific promoter elements directing expression of Cre recombinase. They may be useful in Cre-lox studies of the stomach - such as gastric cancer, digestive disorders, gastric oxidative stress, endocrine-mediated gastric repair, etc.

Detailed description

Parietal cells are epithelial cells in the gastric glands of the stomach that secrete hydrochloric acid (HCl). They contain an extensive secretory network (called canaliculi) from which the HCl is secreted by active transport into the stomach.

The Atp4b-Cre transgene has the parietal cell-specific promoter elements of the ATPase, H+/K+ exchanging, β polypeptide gene (Atp4b) directing expression of a nuclear-localized Cre recombinase (nls-Cre). As such, Cre recombinase expression is highly specific to stomach and, within the stomach, is expressed only in parietal cells and their immediate progenitors. Cre recombinase expression is not reported in gastric enteroendocrine cells. Furthermore, no Cre recombinase activity has been reported in adult kidney, small intestinal and colonic epithelial lineages, or in liver, spleen and lung.

Mice hemizygous for the Atp4b-Cre transgene are viable and fertile with no reported gross physical or behavioral abnormalities. To date (August 2017), it has not been attempted to make this strain homozygous.

 

Development

The Atp4b-Cre transgene was created in the laboratory of Dr. Jeffrey I. Gordon (Washington University in St. Louis). The transgene contained a nuclear localization sequence followed by the Cre recombinase gene (nls-Cre) that was adjoined to regulatory elements of the mouse ATPase, H+/K+ exchanging, beta polypeptide gene (Atp4b; nucleotides -1035 through +24). The nls-Cre sequences were followed by a sequence fragment from the human growth hormone gene (GH1; nucleotides +3 through +2150). Of note, the mRNA product arising from this transgene was designed so that only nls-Cre would be produced. The ~4.25 kbp Atp4b-Cre transgene was used for pronuclear injections into FVB/N oocytes. Founder animals were bred to FVB/N inbred mice, generating two founder lines with germline transmission. Expression testing was performed by breeding some mice to the R26R-lacZ Cre reporter line (see Stock No. 003474) - this identified a single founder line with parietal cell-specific Cre recombinase activity. Mice from this founder line (not bred to the R26R-lacZ Cre reporter) were maintained by breeding with FVB/N mice for several generations. In 2009, Dr. Gordon sent Atp4b-Cre mice on FVB/N genetic background to Dr. Jason C. Mills (Washington University in St. Louis). After a few generations of breeding to FVB/N, Dr. Mills thereafter maintained the Atp4b-Cre colony by breeding with C57BL/6 for ~five years (more than ten generations; the last two years of which were to C57BL/6J). At some point, the mice were also bred to other GFP-expressing mutant mouse lines. In 2017, hemizygous males with black coat color were sent to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Of note, the transgene insertion site(s) and copy number are not known to date (August 2017). Additionally, the donating investigator reports that, at least once during backcrossing, a transgenic female was bred to a C57BL/6 inbred male (thus the Y chromosome of the congenic strain is of C57BL/6 origin).



A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. One of the 43 markers, on Chromosome 1, was segregating with FVB.

Allele

Symbol: Tg(Atp4b-cre)1Jig
Name: transgene insertion 1, Jeffrey I Gordon
MGI accession ID: MGI:3040892
Generation method: Transgenic
Attributes: Recombinase-expressing
Synonyms: HKCre
Marker symbol: Tg(Atp4b-cre)1Jig
Marker name: transgene insertion 1, Jeffrey I Gordon
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Progenitors of acid-producing parietal cells.
Molecular note: Sequence encoding a nuclear localization signal and cre recombinase was adjoined to regulatory elements of the mouse Atp4b gene (nucleotides -1035 through +24). The construct also contained a sequence fragment from the human growth hormone gene (GH1) (nucleotides +3 through +2150). The transgene was expressed in the progenitors of acid-producing parietal cells. Expression was not observed in gastric enteroendocrine cells.