Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   26-NOV-12 Species laboratory mouse Generation N10pN1+F3 (12-FEB-13) Generation Definitions   Donating Investigator Linda Samuelson,   University of Michigan

Description
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.

Development
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.

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cck

011086	C57BL/6-Tg(Cck-cre)CKres/J
012706	STOCK Ccktm1.1(cre)Zjh/J
012710	STOCK Ccktm2.1(cre/ERT2)Zjh/J

View Strains carrying other alleles of Cck     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Cck^tm1Lcs/Cck^tm1Lcs

        involves: 129S1/Sv * 129X1/SvJ

• homeostasis/metabolism phenotype
• abnormal enzyme/ coenzyme level
  • mutants fed a standard chow diet exhibit 60% more pancreatic amylase compared with wild-type, however mutants are viable, fertile, and develop without gross abnormaliteis   (MGI Ref ID J:76894)
• endocrine/exocrine gland phenotype
• abnormal pancreas physiology
  • mutants fed a standard chow diet exhibit 60% more pancreatic amylase compared with wild-type, however mutants are viable, fertile, and develop without gross abnormalities   (MGI Ref ID J:76894)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Diabetes and Obesity Research

Metabolism Research

Reproductive Biology Research

Research Tools
lacZ Expression
Diabetes and Obesity Research
      lacZ

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ccktm1Lcs
Allele Name		targeted mutation 1, Linda C Samuelson
Allele Type		Targeted (Reporter)
Common Name(s)		CCK KO; CcklacZ;
Mutation Made By		Linda Samuelson,   University of Michigan
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
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.
Gene Symbol and Name		Cck, cholecystokinin
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. [MGI Ref ID J:76894]

Genotyping

Genotyping Information

Genotyping Protocols

Cck^tm1Lcs, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lacourse KA; Swanberg LJ; Gillespie PJ; Rehfeld JF; Saunders TL; Samuelson LC. 1999. Pancreatic function in CCK-deficient mice: adaptation to dietary protein does not require CCK. Am J Physiol 276(5 Pt 1):G1302-9. [PubMed: 10330022]  [MGI Ref ID J:76894]

Additional References

Cck^tm1Lcs related

Chen D; Zhao CM; Hakanson R; Samuelson LC; Rehfeld JF; Friis-Hansen L. 2004. Altered control of gastric acid secretion in gastrin-cholecystokinin double mutant mice. Gastroenterology 126(2):476-87. [PubMed: 14762785]  [MGI Ref ID J:90495]

Friis-Hansen L. 2006. Achlorhydria is associated with gastric microbial overgrowth and development of cancer: lessons learned from the gastrin knockout mouse. Scand J Clin Lab Invest 66(7):607-21. [PubMed: 17101553]  [MGI Ref ID J:128734]

Friis-Hansen L; Wierup N; Rehfeld JF; Sundler F. 2005. Reduced ghrelin, islet amyloid polypeptide, and peptide YY expression in the stomach of gastrin-cholecystokinin knockout mice. Endocrinology 146(10):4464-71. [PubMed: 16002530]  [MGI Ref ID J:101574]

Hannibal J; Hundahl C; Fahrenkrug J; Rehfeld JF; Friis-Hansen L. 2010. Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice. Eur J Neurosci 32(6):1006-17. [PubMed: 20731710]  [MGI Ref ID J:171775]

Jain RN; Samuelson LC. 2007. Transcriptional profiling of gastrin-regulated genes in mouse stomach. Physiol Genomics 29(1):1-12. [PubMed: 17105752]  [MGI Ref ID J:119252]

Lavine JA; Raess PW; Stapleton DS; Rabaglia ME; Suhonen JI; Schueler KL; Koltes JE; Dawson JA; Yandell BS; Samuelson LC; Beinfeld MC; Davis DB; Hellerstein MK; Keller MP; Attie AD. 2010. Cholecystokinin is up-regulated in obese mouse islets and expands beta-cell mass by increasing beta-cell survival. Endocrinology 151(8):3577-88. [PubMed: 20534724]  [MGI Ref ID J:163942]

Lay JM; Gillespie PJ; Samuelson LC. 1999. Murine prenatal expression of cholecystokinin in neural crest, enteric neurons, and enteroendocrine cells. Dev Dyn 216(2):190-200. [PubMed: 10536058]  [MGI Ref ID J:57954]

Lo CC; Langhans W; Georgievsky M; Arnold M; Caldwell JL; Cheng S; Liu M; Woods SC; Tso P. 2012. Apolipoprotein AIV requires cholecystokinin and vagal nerves to suppress food intake. Endocrinology 153(12):5857-65. [PubMed: 23027805]  [MGI Ref ID J:192373]

Lo CM; Obici S; Dong HH; Haas M; Lou D; Kim DH; Liu M; D'Alessio D; Woods SC; Tso P. 2011. Impaired insulin secretion and enhanced insulin sensitivity in cholecystokinin-deficient mice. Diabetes 60(7):2000-7. [PubMed: 21602512]  [MGI Ref ID J:186753]

Lo CM; Samuelson LC; Chambers JB; King A; Heiman J; Jandacek RJ; Sakai RR; Benoit SC; Raybould HE; Woods SC; Tso P. 2008. Characterization of mice lacking the gene for cholecystokinin. Am J Physiol Regul Integr Comp Physiol 294(3):R803-10. [PubMed: 18160529]  [MGI Ref ID J:131943]

Wang HH; Portincasa P; Liu M; Tso P; Samuelson LC; Wang DQ. 2010. Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice. Biochim Biophys Acta 1801(2):138-46. [PubMed: 19836465]  [MGI Ref ID J:164830]

Worthington JJ; Samuelson LC; Grencis RK; McLaughlin JT. 2013. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion. PLoS Pathog 9(1):e1003122. [PubMed: 23349631]  [MGI Ref ID J:195851]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.
Mating System	Homozygote x Homozygote         (Female x Male)   26-NOV-12

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

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.

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