Homozygous Cckartm1Kpn knock-out mice exhibit larger gallbladder volumes and impaired gastric function, 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 pancreatic membranes. Mice homozygous for the targeted mutation do not exhibit decreased food intake due to peritoneal injection of cholecystokinin. Baseline food and water intake and body weight is normal in mutant mice. These mutant mice have larger gallbladder volumes and are more likely to develop spontaneous gallstones than wildtype controls. Gastric function is impaired due to diminished intestinal lipid feedback response. Small-intestine transit time is increased in mutant mice. When fed a lithogenic diet, mutant mice have an increase in biliary cholesterol secretion rates, when compared to the wildtype. Although the total number of olfactory-gonadotropin-releasing hormone-1 neuroendocrine (GnRH-1)neurons is the same in embryonic day 14.5 aged mutant and wildtype mice, more GnRH-1 neurons are found in the forebrain of the mutant than in the wildtype. This mutant mouse strain may be useful in studies of the neuroendocrine and gastrointestinal systems, and lipid metabolism.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to 129/SvEv mice. The mice were then crossed to 129S1/SvImJ for one generation. Heterozygotes were then crossed to generate homozygotes.
|Allele Name||targeted mutation 1, Alan S Kopin|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CCK1R-; CCK-1R-; CCK-AR-|
|Gene Symbol and Name||Cckar, cholecystokinin A receptor|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A PGK-neo replaced exon 3, which encodes a portion of the third transmembrane domain and the second intracellular loop including the "ERY" motif. Southern blot of mutant mice indicated successful recombination. Testing for 125I-CCK-8 binding in pancreatic membranes mutant mice indicated showed no displaceable binding and therefore a lack a Cckar receptors.|
|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-AR KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006367 in your Materials and Methods section.