Overview

Also Known As:C3-

These C3 knockout mice exhibit an increased susceptibility to lethal infection by Group B streptococci, reductions in peritoneal mast cell degranulation, defects in antibody response to T cell dependent antigens and a failure in isotype switching.

Donating Investigator

Gloria Koo, Hospital for Special Surgery

Genetic overview

Genetic Background	Generation

C3^tm1Hrc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	C3	complement component 3

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools

View All Research Applications

Details

Detailed Description

Mice homozygous for the C3 (complement component C3) targeted mutation are viable and fertile. Homozygous mutants exhibit an increased susceptibility to lethal infection by Group B streptococci. Reductions in peritoneal mast cell degranulation, production of tumor necrosis factor alpha, neutrophil infiltration and bacterial clearance have also been reported in these mice. Homozygotes also demonstrate a profound defect in antibody response to T cell dependent antigens. They show a diminished level of peanut agglutin+ germinal centers and a failure in isotype switching despite normal B cell signalling in vitro.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

The C3 gene is disrupted by PGK/Neo cassette. Approximately 600 nt of the gene are deleted. A portion of these nts (nt 1850-2214; AA 620-741, pro-C3 numbering) fall within the coding region. The targeting construct was transfected into 129S4/SvJae derived J1 ES cells. Successful transfectants were injected into 3.5 day old C57BL/6 blastocysts which were then implanted into the uterus of pseudopregnant females. Male chimeric mice were bred with C57BL/6 females. The mice were backcrossed to C57BL/6J for 5 generations. The mice were then crossed to CBA/J for 6 generations.

Control Suggestions

000656 CBA/J

Additional Information

Considerations for Choosing Controls

Genetics

C3^tm1Hrc

Allele Symbol: C3^tm1Hrc

Allele Name	targeted mutation 1, Harvey R Colten
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	C3-
Gene Symbol and Name	C3, complement component 3
Gene Synonym(s)
Strain of Origin	129/Sv
Chromosome	17
General Note	ES cell line = RW4 (129X1/SvJ) or D3 (129S2/SvPas).
Molecular Note	A genomic fragment containing 2.3 kb of the 5' flanking region and the first 105 bp of exon 1 was replaced with a neomycin selection cassette. Northern blot analysis on liver RNA derived from homozygous mice demonstrated that no detectable transcript was produced in this tissue; however, a full length transcript was detected in lung, kidney, epididymal fat tissue, spleen and heart.
Mutations Made By	Michael Carroll, The Center for Blood Research

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

complement component 3 deficiency

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - specific complement deficiency
- Inflammation
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - specific complement deficiency

Mammalian Phenotype Terms by Genotype

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

Genotype: C3^tm1Hrc/C3^tm1Hrc
either: (involves: 129S2/SvPas * C57BL/6) or (involves: 129X1/SvJ * C57BL/6)

immune system phenotype

increased susceptibility to bacterial infection
- a 2000-fold increase in pneumococci is seen compared to wild-type littermates following infection with S. pneumoniae

Genotype: C3^tm1Hrc/C3^tm1Hrc
involves: 129/Sv * C57BL/6

adipose tissue phenotype

decreased total body fat amount
- a small but significant decrease in adipose tissue mass particularly in the gonadal and perirenal fat is seen in male mutants
- on a high or low fat diet total body fat is decreased by 40% or 59%, respectively, in female mutants

decreased white adipose tissue amount
- on a high or low fat diet female mutants have decreased white adipose tissue

increased brown adipose tissue amount
- a significant increase in capsular BAT is seen on high and low fat diets in male mutants compared to wild-type

behavior/neurological phenotype

polyphagia
- mild polyphagia is seen in male mutants
- on a high fat diet a marked increase in food intake is seen in female mutants compared to wild-type littermates

growth/size/body region phenotype

decreased body weight
- on a high or low fat diet female mutants weigh less than wild-type littermates

homeostasis/metabolism phenotype

abnormal energy expenditure
- male mutants require a greater caloric intake relative to body weight gained compared to wild-type littermates
- the average calorie intake/g increase in body weight is greater in female mutants on either a high or low fat diet

abnormal glucose homeostasis

abnormal lipid homeostasis

decreased circulating glucose level
- at any given insulin level the corresponding glucose level is significantly lower in male mutants compared to wild-type on a high fat diet
- glucose levels and the glucose level for any given insulin level are significantly decreased in female mutants

decreased circulating insulin level
- insulin levels are significantly decreased in female mutants

decreased circulating leptin level
- on a high or low fat diet, relative to body weight leptin levels are reduced in female mutants
- relative to body weight leptin levels are reduced in male mutants

decreased circulating triglyceride level
- on either a high or low fat diet postprandial triglyceride levels are reduced in female mutants compared to wild-type littermates

increased circulating free fatty acid level
- after 4 months on a low fat or high fat diet a greater increase in non-esterified fatty acid levels is seen in male mutants compared to wild-type mice
- on a high fat diet postprandial plasma non-esterified fatty acid levels are increased 2.5 fold compared to male mutants on a low fat diet and no such increase was seen in wild-type littermates
- postprandial but not fasting non-esterified fatty acid levels are increased in female mutants especially at 26 weeks of age

increased triglyceride level
- a larger increase in triglyceride levels is seen in male mutants compared to wild-type littermates after 4 months on a low fat diet but not on a high fat diet
- an 80% increase in triglyceride levels compared to wild-type mice is seen in male mutants after eating (postprandial)

Genotype: C3^tm1Hrc/C3^tm1Hrc
involves: 129

adipose tissue phenotype

decreased total body fat amount

behavior/neurological phenotype

polyphagia
- mutants consume 30% more calories compared to wild-type mice

digestive/alimentary phenotype

abnormal intestinal lipid absorption
- muscle and liver uptake of labeled oleate is increased after fat loading however brown adipose tissue oleate uptake is decreased

growth/size/body region phenotype

decreased body weight

homeostasis/metabolism phenotype

abnormal intestinal lipid absorption
- muscle and liver uptake of labeled oleate is increased after fat loading however brown adipose tissue oleate uptake is decreased

decreased circulating insulin level
- insulin levels are decreased relative to glucose compared to wild-type mice

decreased circulating leptin level

increased circulating free fatty acid level
- in males non-esterified fatty acid clearance is delayed relative to wild-type mice after fat administration

increased triglyceride level
- triglyceride clearance is delayed in mutants backcrossed onto a 129/Sv background but not a C57BL/6 background

Genotype: C3^tm1Hrc/C3^tm1Hrc
B6.129-C3

immune system phenotype

impaired complement alternative pathway
- mice treated with collagen antibodies do not exhibit C43 or C5a depositions compared unlike similarly treated wild-type mice

liver/biliary system phenotype

decreased liver regeneration
- hepatocyte proliferation is reduced and removal of necrotic and apoptotic cells is impaired after CCl₄ treatment

References

Additional - C3^tm1Hrc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:C3
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygotes. Donating Investigator maintained as homozygote.
- Additional Breeding and Husbandry Support
Citation
When using the C3- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32042 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

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. 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

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Questions about Terms of Use

Licensing Information

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Also Known As:C3-

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

C3tm1Hrc

Allele Symbol: C3tm1Hrc

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: C3tm1Hrc/C3tm1Hrceither: (involves: 129S2/SvPas * C57BL/6) or (involves: 129X1/SvJ * C57BL/6)

immune system phenotype

Genotype: C3tm1Hrc/C3tm1Hrcinvolves: 129/Sv * C57BL/6

adipose tissue phenotype

behavior/neurological phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: C3tm1Hrc/C3tm1Hrcinvolves: 129

adipose tissue phenotype

behavior/neurological phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: C3tm1Hrc/C3tm1HrcB6.129-C3

immune system phenotype

liver/biliary system phenotype

References

Additional - C3tm1Hrc related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

C3^tm1Hrc

Allele Symbol: C3^tm1Hrc

Genotype: C3^tm1Hrc/C3^tm1Hrc
either: (involves: 129S2/SvPas * C57BL/6) or (involves: 129X1/SvJ * C57BL/6)

Genotype: C3^tm1Hrc/C3^tm1Hrc
involves: 129/Sv * C57BL/6

Genotype: C3^tm1Hrc/C3^tm1Hrc
involves: 129

Genotype: C3^tm1Hrc/C3^tm1Hrc
B6.129-C3

Additional - C3^tm1Hrc related