These double Cckartm1Kpn, Cckbrtm1Kpn knock-out mice have the combined phenotype of the individual knock-outs (Stock No. 006367 and Stock No. 006369 respectively), and may be useful in applications relating to gastrointestinal studies.
Alan S Kopin, Tufts-New England Medical Center
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Cckbr | cholecystokinin B receptor |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Cckar | cholecystokinin A receptor |
Mice that are homozygous for both of the targeted mutations are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The donating investigator reports that the double mutants have a combined phenotype.
No CCKBR 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 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.
No CCKAR receptor function was detected in competition binding assay of pancreatic membranes. Homozygotes 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, lipid metabolism, gastric differentiation, hypochlorhydria and hypergastinemia.
For the Cckar targeted mutation, a targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3. The construct was electroporated into 129-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.
For the Cckbr targeted mutation, 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.
The two single targeted mutation strains, 129-Cckartm1Kpn/J (Stock No. 6367) and 129-Cckbrtm1Kpn/J (Stock No. 6369), were then crossed to generate the double targeted mutation line.
Allele Name | targeted mutation 1, Alan S Kopin |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Cckbr, cholecystokinin B receptor |
Gene Synonym(s) | |
Strain of Origin | 129S2/SvPas |
Chromosome | 7 |
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 |
Allele Name | targeted mutation 1, Alan S Kopin |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | CCK1R-; CCK-1R-; CCK-AR- |
Gene Symbol and Name | Cckar, cholecystokinin A receptor |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 5 |
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 for both targeted mutations.
When using the ABKO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006365 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Cckar<tm1Kpn>, Heterozygous for Cckbr<tm1Kpn> |
Frozen Mouse Embryo | 129-Cckar<tm1Kpn> Cckbr<tm1Kpn>/J | $2595.00 |
Frozen Mouse Embryo | 129-Cckar<tm1Kpn> Cckbr<tm1Kpn>/J | $2595.00 |
Frozen Mouse Embryo | 129-Cckar<tm1Kpn> Cckbr<tm1Kpn>/J | $3373.50 |
Frozen Mouse Embryo | 129-Cckar<tm1Kpn> Cckbr<tm1Kpn>/J | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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