Overview

Homozygotes are resistant to heat-stable enterotoxin (STa)-induced diarrhea and to enterotoxigenic bacteria that produce STa. Cholera toxin, however, causes diarrhea. These mice may be useful in studies of enteric infection.

Donating Investigator

David L. Garbers, U.T. Southwestern Medical Center

Genetic overview

Genetic Background	Generation

Gucy2c^tm1Gar

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Gucy2c	guanylate cyclase 2c

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this targeted mutation are viable and fertile and do not display any gross physical or behavioral abnormalities. They are resistant to heat-stable enterotoxin (STa)-induced diarrhea and to enterotoxigenic bacteria that produce STa. Cholera toxin, however, causes diarrhea. Expression is not detected by Western blot analysis of intestinal mucosal preparations. These mice may be useful in studies of enteric infection.

Development

A targeting vector was designed to insert a neomycin resistance cassette under the control of a Pol II promoter (in the opposite transcriptional orientation) in exon 1 of the gene. The targeting vector was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Targeted ES cells were injected into C57BL/6 blastocysts. Male chimeras were crossed to C57BL/6J or Black Swiss females.

Selected References

Schulz S; Lopez MJ; Kuhn M; Garbers DL. 1997. Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice. J Clin Invest 100(6):1590-5PubMed: 9294128 MGI: J:43046

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Genetics

Gucy2c^tm1Gar

Allele Symbol: Gucy2c^tm1Gar

Allele Name	targeted mutation 1, David L Garbers
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	GC-C -; Gcc^-
Gene Symbol and Name	Gucy2c, guanylate cyclase 2c
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	6
Molecular Note	Exon 1 was disrupted by a neomycin selection cassette inserted by homologous recombination. Protein was undetected by Western blot analysis of intestinal mucosal scrapings obtained from homozygous mutant mice. Total intestine mucosal guanylyl cyclase activity was reduced 16-fold relative to wild-type controls, whereas heat-stable enterotoxin (STa)-stimulable guanylyl cyclase activity was absent in mutant mice.
Mutations Made By	David Garbers, U.T. Southwestern Medical Center

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

obesity

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

abdominal obesity-metabolic syndrome

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Gucy2c^tm1Gar/Gucy2c^tm1Gar
B6.129S6-Gucy2c

adipose tissue phenotype

increased subcutaneous adipose tissue amount

increased total body fat amount
- mutants exhibit an accumulation of adipose mass, including an increase in visceral and subcutaneous fat compartments

homeostasis/metabolism phenotype

impaired glucose tolerance
- impaired glycemic control

increased circulating insulin level
- fasted serum concentrations of 12 months old mutants raised on a high caloric diet are increased compared to wild-type mice on the same diet

increased circulating leptin level
- fasted serum leptin levels are increased at 10-12 and 18 months of age in mutants raised on either the low calorie or high calorie diet

increased liver triglyceride level
- mice raised on a low calorie diet exhibit increased hepatic triglyceride content

integument phenotype

increased subcutaneous adipose tissue amount

liver/biliary system phenotype

hepatic steatosis

increased liver triglyceride level
- mice raised on a low calorie diet exhibit increased hepatic triglyceride content

behavior/neurological phenotype

increased compensatory feeding amount
- fasted and refed mutants display deficient postprandial satiation

polyphagia
- Normal - the probable cause of the excess adiposity
- Normal - however, mutants exhibit normal lipid digestion, lipid absorption, distribution and clearance, normal energy mobilization and expenditure, normal circadian cycles and thermoregulatory reflexes to cold, indicating that an increase in caloric consumption is the probable cause of the excess adiposity
- mutants are hyperphagic, independent of sex, dietary nutrients, or dietary caloric content

cardiovascular system phenotype

cardiac hypertrophy
- mean heart size in mice raised on either the low calorie or high calorie diet is increased compared to wild-type mice

increased heart weight

growth/size/body region phenotype

cardiac hypertrophy
- mean heart size in mice raised on either the low calorie or high calorie diet is increased compared to wild-type mice

increased body weight
- females raised on the high calorie diet showed the highest weight increase, with mutants being 26.3% heavier than wild-type mice
- mutants raised on a standard low calorie diet, moderate calorie diet, or high calorie diet exhibit an increased body weight compared to wild-type mice

increased heart weight

The following phenotype relates to a compound genotype created using this strain

Genotype: Gucy2c^tm1Gar/Gucy2c^tm1Gar
either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6J)

digestive/alimentary phenotype

diarrhea
- following oral inoculation with 5 ug of cholera toxin, suckling homozygotes show normal fluid accumulation within the intestine (diarrhea), as determined by gut/carcass weight ratio

immune system phenotype

decreased susceptibility to bacterial infection
- following an oral inoculum of 10 U of E. coli heat-stable enterotoxin, 3-day suckling homozygotes failed to exhibit any fluid accumulation within the intestinal lumen, as determined by gut/carcass weight ratio
- following inoculation with enterotoxigenic E. coli strain 1676 by gavage, homozygotes failed to develop signs of diarrhea, indicating resistance to enterotoxigenic bacteria that produce heat stable enteroxins
- in contrast, suckling homozygotes showed normal fluid accumulation within the intestine following oral inoculation with 5 ug of cholera toxin

decreased susceptibility to bacterial infection induced morbidity/mortality
- following inoculation with a human enterotoxigenic E. coli strain (H10407) which does not colonize and infect mice, 23 of 26 homozygotes survived to weaning, while the remaining 3 died within 24 hrs of the gavage
- following inoculation with enterotoxigenic E. coli strain 1676 by gavage, most homozygotes survived to weaning, whereas all wild-type and heterozygous controls died within 72 hrs of infection
- only a small minority of homozygotes died within 24-72 hrs of administration of E. coli strain 1676; however, no diarrhea was observed and no cause of death was established

mortality/aging

decreased susceptibility to bacterial infection induced morbidity/mortality
- following inoculation with a human enterotoxigenic E. coli strain (H10407) which does not colonize and infect mice, 23 of 26 homozygotes survived to weaning, while the remaining 3 died within 24 hrs of the gavage
- following inoculation with enterotoxigenic E. coli strain 1676 by gavage, most homozygotes survived to weaning, whereas all wild-type and heterozygous controls died within 72 hrs of infection
- only a small minority of homozygotes died within 24-72 hrs of administration of E. coli strain 1676; however, no diarrhea was observed and no cause of death was established

References

Schulz S; Lopez MJ; Kuhn M; Garbers DL. 1997. Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice. J Clin Invest 100(6):1590-5PubMed: 9294128 MGI: J:43046

Additional - Gucy2c^tm1Gar related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Gucy2c
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, heterozygotes or homozygotes may be bred.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Gucy2c^tm1Gar/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #007660 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Gucy2c<tm1Gar>

Related Products and Services

Frozen Mouse Embryo	STOCK Gucy2c<tm1Gar>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Gucy2c<tm1Gar>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Gucy2c<tm1Gar>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	STOCK Gucy2c<tm1Gar>/J Frozen Embryo	$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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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Gucy2ctm1Gar

Allele Symbol: Gucy2ctm1Gar

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Gucy2ctm1Gar/Gucy2ctm1GarB6.129S6-Gucy2c

adipose tissue phenotype

homeostasis/metabolism phenotype

integument phenotype

liver/biliary system phenotype

behavior/neurological phenotype

cardiovascular system phenotype

growth/size/body region phenotype

Genotype: Gucy2ctm1Gar/Gucy2ctm1Gareither: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6J)

digestive/alimentary phenotype

immune system phenotype

mortality/aging

References

Additional - Gucy2ctm1Gar related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Gucy2c^tm1Gar

Allele Symbol: Gucy2c^tm1Gar

Genotype: Gucy2c^tm1Gar/Gucy2c^tm1Gar
B6.129S6-Gucy2c

Genotype: Gucy2c^tm1Gar/Gucy2c^tm1Gar
either: (involves: 129S6/SvEvTac * Black Swiss) or (involves: 129S6/SvEvTac * C57BL/6J)

Additional - Gucy2c^tm1Gar related