Mice homozygous for a null Atp4a (H+/K+ exchanging, gastric ATPase, alpha polypeptide) allele lack stomach acid secretion (achlorhydria) and exhibit hypergastrinemia and gastric metaplasia. This strain may be useful for studying secretory membrane biogenesis and the role of parietal cells in gastric mucosa development and maintenance.
Gary E Shull, University of Cincinnati
Atp4a (H+/K+ exchanging, gastric ATPase, alpha polypeptide) encodes the alpha-subunit of a P-type ATPase (gastric proton pump) found in membranes of the gastric parietal cell. Homozygous mice are viable, fertile, and normal in size. Mice lack stomach acid secretion (achlorhydria) and exhibit hypergastrinemia and gastric metaplasia. Parietal cells have dilated canaliculi, and lack typical cannicular microvilli and tubulovesicles. This strain may be useful for studying secretory membrane biogenesis and the role of parietal cells in gastric mucosa development and maintenance.
A targeting vector was designed to replace codons 360-390 in exon 8 with the neomycin resistance gene, abolishing the catalytic phosphorylation site required for enzyme activity. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to Black Swiss mice and offspring were backcrossed to C57BL/6 more than 10 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Gary E Shull|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Atp4a, ATPase, H+/K+ exchanging, gastric, alpha polypeptide|
|Strain of Origin||129X1/SvJ|
|Molecular Note||A part of exon 8 encoding amino acids 360-390 was replaced with a neomycin selection cassette. Northern blot analysis demonstrated that no detectable full length transcript was produced from this allele in stomach of homozygous mice, although trace levels of a shorter 1 kb transcript was detected. Immunocytochemistry experiments on stomach tissue of homozygous mice demonstrated that no detectable protein was present.|
|Mutations Made By|| |
Gary Shull, University of Cincinnati
While maintaining a live colony, these mice are bred as homozygotes.
When using the B6.129X1(Cg)-Atp4atm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36712 in your Materials and Methods section.