Strain Name: |
C3Fe.B6-Mcm4chaos3/J |
|---|---|
Stock Number: |
006863 |
Availability: | Repository- Live |
General Terms and Conditions |
| Genes & Alleles | Mcm4; Mcm4chaos3; |
Type JAX® GEMM® Strain - Chemically Induced Mutation Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Congenic Type JAX® GEMM® Strain - Mutant Strain Species laboratory mouse Donating Investigator John Schimenti, Cornell University Generation N8pN1 (20-DEC-07) Strain 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.Strain 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.
Mammalian Phenotype Terms assigned by genotype |
| Allele Symbol | Mcm4chaos3 | ||
|---|---|---|---|
| Allele Name | chromosomal aberration occurring spontaneously 3 | ||
| 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] | ||
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| 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. |
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| Diet Information | LabDiet® 5K52/5K67 |
Congenic Nomenclature
Room Number AX11
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
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]
| Strain Name: | C3Fe.B6-Mcm4chaos3/J |
| Stock Number: | 006863 |
IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.
| 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. |
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| Supply Notes |
Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. |
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