Description

Strain Information

Type Chemically Induced Mutation; Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N8pN1 (20-DEC-07)   Donating Investigator John Schimenti,   Cornell University

Description
Mice homozygous for this ENU-induced F345I hypomorphic allele (Chaos3) are viable, fertile, and overtly indistinguishable from normal littermates. Homozygous, but not heterozygous, mice have slightly reduced wildtype protein levels in mouse embryonic fibroblasts (MEFs). Whereas Chaos3 heterozygotes show mildly elevated (2- to 5-fold) micronucleus frequencies compared with wildtype, homozygotes have an approximate 20-fold increase with over 7% of erythrocytes containing micronuclei. MEFs from homozygous mice exhibit mild defects (cell proliferation, S phase and G2/M populations), and are highly susceptible to chromosome breakage following treatment with the DNA replication inhibitor aphidicolin. On a congenic C3HeB/FeJ background, greater than 80% of homozygous females exhibit mammary adenocarcinomas with a mean latency of 12 months, while males have no tumor incidence. These Chaos3 mice provide a novel, non-transgenic model of breast cancer, and may be useful for studying of diagnostic pre-cancer cell markers, chromosomal instability and cell cycle checkpoint responses.

Development
Male C57BL/6J mice (Stock No. 000664) were treated with multidose N-ethyl-N-nitrosourea (ENU) and then bred to C3HeB/FeJ (Stock No. 000658). The resulting male pups were then bred to C3HeB/FeJ females to obtain second generation mice, which were subsequently intercrossed to obtain third generation mice. A mutagenesis screen was then performed to select mice for chromosome instability (as assessed by micronucleus levels in erythrocytes). One of these mutants in which the tendency to form micronuclei segregated in a monogenic, autosomal recessive manner was termed Chaos3 (or chromosome aberrations occurring spontaneously 3). Further studies revealed that Chaos3 is a hypomorphic allele of Mcm4, containing a T to A transversion at nucleotide 1033 of the coding region that defines an amino acid change from phenylalanine to isoleucine at residue 345 (F345I). These mice have been backcrossed to C3HeB/FeJ for at least 8 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Mcm4^chaos3/Mcm4^chaos3

        C3.B6-Mcm4^chaos3

• tumorigenesis
• increased tumor incidence (MGI Ref ID J:117494)
  • females (majority are virgin) show a high susceptibility to development of mammary tumors
• hepatocellular carcinoma (MGI Ref ID J:117494)
  • 1 female developed a hepatocellular carcinoma
• lung adenocarcinoma (MGI Ref ID J:117494)
  • 2 mammary tumors metastasized to lung
• mammary adenocarcinoma (MGI Ref ID J:117494)
  • 13/16 females develop mammary tumors with a latency of 12 months; five animals had more than one tumor
  • 9/18 tumors were in thoracic mammary gland and 7/18 were in cervical mammary gland

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

Mcm4^chaos3/Mcm4⁺

        involves: C57BL/6J

• cellular phenotype
• abnormal nucleus morphology (MGI Ref ID J:117494)
  • show 2- to 5-fold elevated micronucleus frequencies compared to wild-type

Mcm4^chaos3/Mcm4^chaos3

        involves: C57BL/6J

• cellular phenotype
• abnormal nucleus morphology (MGI Ref ID J:117494)
  • show 20-fold elevated micronucleus frequencies compared to wild-type
• hematopoietic system phenotype
• abnormal erythrocyte morphology (MGI Ref ID J:117494)
  • >7% of erythrocytes contain micronuclei

Mcm4^chaos3/Mcm4^chaos3

        involves: C3HeB/FeJ * C57BL/6J

• cellular phenotype
• abnormal cell cycle (MGI Ref ID J:117494)
  • there are a lower number of cells in S phase and slightly increased G2/M populations compared to controls
• decreased cell proliferation (MGI Ref ID J:117494)
  • mouse embryonic fibroblasts (MEFs) show a mild defect in proliferation

View Research Applications

Research Applications

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

Cancer Research
Increased Tumor Incidence (Adenomas)
Increased Tumor Incidence (Mammary Gland Tumors)
Increased Tumor Incidence (Mammary Gland Tumors: females only)
Other (DNA Repair)
Other (tumor metastasis)
Tumor Suppressor Genes

Cell Biology Research
Cell Cycle Regulation
DNA Damage Response
Transcriptional Regulation

Hematological Research
Hematopoietic Defects

Research Tools
Cancer Research
Cell Biology Research
Hematological Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Mcm4chaos3
Allele Name		chromosomal aberration occurring spontaneously 3
Allele Type		Chemically induced (ENU)
Common Name(s)		Chaos3; Mcm4F345I;
Mutation Made By		John Schimenti,   Cornell University
Strain of Origin		C57BL/6J
Gene Symbol and Name		Mcm4, minichromosome maintenance deficient 4 homolog (S. cerevisiae)
Chromosome		16
Gene Common Name(s)		19G; AI325074; AU045576; CDC21; CDC54; Cdc21; MGC33310; Mcmd4; P1-CDC21; cell division cycle 21 (S.pombe); expressed sequence AI325074; expressed sequence AU045576; hCdc21; mcdc21; mini chromosome maintenance deficient 4 homolog (S. cerevisiae);
Molecular Note		In an ENU mutagenesis screen, a de novo T->A transversion at nucleotide 1033 of the coding region occurred, creating a phenylalanine to isoleucine change at residue 345. [MGI Ref ID J:117494]

Genotyping

Genotyping Information

Genotyping Protocols

Mcm4^chaos3, PYRO, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Shima N; Alcaraz A; Liachko I; Buske TR; Andrews CA; Munroe RJ; Hartford SA; Tye BK; Schimenti JC. 2007. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nat Genet 39(1):93-8. [PubMed: 17143284]  [MGI Ref ID J:117494]

Shima N; Hartford SA; Duffy T; Wilson LA; Schimenti KJ; Schimenti JC. 2003. Phenotype-based identification of mouse chromosome instability mutants. Genetics 163(3):1031-40. [PubMed: 12663541]  [MGI Ref ID J:82700]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice are bred to C3HeB/FeJ (Stock No. 000658) inbred mice or wildtype siblings. Homozygous mutant females develop mammary turmors with a high incidence by approximately one year of age. Breeding productivity in heterozygous female may decline with age.
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

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