The cholecystokinin gene is disrupted by the insertion of a β-geo fusion cassette in these knockin/knockout mice. LacZ is detected in the gut and brain, and homozygotes exhibit a range of metabolic and behavioral defects.
Linda Samuelson, University of Michigan
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Cck | cholecystokinin |
A β-geo fusion cassette was inserted into exon 2 of the cholecystokinin (Cck) gene, abolishing gene function. Cholecystokinin is a gastrointestinal satiety hormone secreted by enteroendocrine intestinal I cells in response to fat and protein. Its release stimulates pancreatic enzyme secretion, modulates intestinal motility, and regulates meal size in the central nervous system. CCK is also a neurotransmitter released by subpopulations of neurons in the central nervous system, where it influences both memory and exploratory behaviors. Homozygous CCK-/- mice are viable, fertile, and normal in size, with lacZ staining visible in the gut and brain. Specifically, lacZ expression is evident in the neural tube, neural crest, mid- and hindbrain, and heart (E8.5-9.5), from the proximal stomach into the colon (E10.5-15.5), and persists in scattered endocrine cells in the upper intestine in adults. Expression is also evident in the cortex, hippocampus, and thalamus of adult mice. On a high fat diet, these mice gain less weight, have less fat mass, and absorb less total fat than wildtype mice. They have higher energy expenditure, enhanced insulin sensitivity, and decreased glucose tolerance than control mice, with no change to triglyceride, cholesterol, glucose and insulin levels. These CCK-/- mice exhibit impaired glucose-stimulated insulin secretion with no change in islet size, number, or morphology. Pancreatic amylase levels are 60% higher in these mice and they have a higher frequency of gall stones than wildtype mice. They also display spatial learning and memory defects, with reduced exploratory and increased anxiety-related behaviors.
A targeting vector was designed to insert a neomycin-β-galactosidase fusion protein (β-geo) into exon 2 of the cholecystokinin (Cck) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to 129/SvJ females. These mice were then backcrossed at least 10 generations to C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | lacZ expression is evident in the neural tube, neural crest, mid- and hindbrain, and heart (E8.5-9.5), from the proximal stomach into the colon (E10.5-15.5), and persists in scattered endocrine cells in the upper intestine in adults. Expression is also evident in the cortex, hippocampus, and thalamus of adult mice. |
Allele Name | targeted mutation 1, Linda C Samuelson |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | CCK KO; CcklacZ |
Gene Symbol and Name | Cck, cholecystokinin |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | lacZ expression is evident in the neural tube, neural crest, mid- and hindbrain, and heart (E8.5-9.5), from the proximal stomach into the colon (E10.5-15.5), and persists in scattered endocrine cells in the upper intestine in adults. Expression is also evident in the cortex, hippocampus, and thalamus of adult mice. |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 9 |
Molecular Note | A cassette containing a lacZ-neo fusiong gene was inserted into exon 2 to delete 168 nucleotides encoding the amino-terminal signal sequence in exon 2. Radioimmunoassays of brain and duodenum tissue from homozygous mutant mice showed an absence of bioactive protein product. |
Mutations Made By | Linda Samuelson, University of Michigan |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129-Ccktm1Lcs/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017710 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Cck<tm1Lcs> |
Frozen Mouse Embryo | B6.129-Cck<tm1Lcs>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129-Cck<tm1Lcs>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129-Cck<tm1Lcs>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129-Cck<tm1Lcs>/J Frozen Embryo | $3373.50 |
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