Homozygous Cckbrtm1Kpn knock-out mice exhibit a marked increase in basal gastric pH and an elevation of plasma gastrin concentration, and may be useful in applications relating to gastrointestinal studies.
Alan S Kopin, Tufts-New England Medical Center
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No receptor function was detected in competition binding assay of brain (cerebral plasma) membranes. When compared to wildtype, gastric pH in homozygotes is higher, pH 5.2, after overnight fast. Histological analysis reveals diminished parietal cell, enterochromaffin-like cell (ECL) and antral comatostatin-producing D cell densities. An increase in the number of gastrin-producing G cells is observed. There is an increased number of H+, K+ -ATPase immunoreactive negative cells and abnormal distribution of parietal cells in oxyntic glands. Circulating gastrin levels are 10-fold higher in homozygotes. Gastric mucosal histamine levels are greatly reduced and histamine-immunoreactive ECL cells are absent. This mutant mouse strain may be useful in studies of hypochlorhydria, hypergastinemia, gastric antral endocrine regulation, and gastric differentiation.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Heterozygous progeny from chimeras were crossed to produce homozygotes. The mice were then crossed to 129S1/SvImJ for one generation. Resulting heterozygotes were crossed to generate homozygotes.
|Allele Name||targeted mutation 1, Alan S Kopin|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Cckbr, cholecystokinin B receptor|
|Strain of Origin||129S2/SvPas|
|Molecular Note||The insertion of a neomycin selection cassette deleted sequence encoding transmembrane domains V through VII, which are essential for structure. Radiolabeled binding experiments of cerbral plasma membranes isolated from homozygous mutant mice confirmed a lack of functional protein.|
|Mutations Made By|| |
Alan Kopin, Tufts-New England Medical Center
When maintaining a live colony, these mice can be bred as homozygotes.
When using the CCK-BR KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006369 in your Materials and Methods section.