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| These Col1a1-tetO-Dnmt3b1::R26-M2rtTA mice may be used to regulate expression of Dnmt3b1 via a tetracycline-controlled transactivator protein system, and may be useful in studying the regulation of tumorigenesis. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
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Description
Strain Information
Former Names B6.Cg-Col1a1tm9(tetO-Dnmt3b1_i1)Jae/J (Changed: 06-APR-12 ) B6.129S4-Col1a1tm9(tetO-Dnmt3b1)Jae/J (Changed: 29-MAR-12 ) 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) 25-FEB-13 Species laboratory mouse Generation N7+N1 (18-JUL-12)
Generation DefinitionsDonating Investigator Dr. Rudolf Jaenisch, Whitehead Institute (MIT) Description
Mice homozygous for the Col1a1-tetO-Dnmt3b1 targeted mutation are viable and fertile. Expression of the DNA methyltransferase 3B gene (Dnmt3b1) is controlled by the tet-responsive element (tetO). DNMT3B1 is a de novo methyltransferase which is able to methylate CpG sequences, a required step during development. Hypermethylation of DNA has been implicated in many neoplasms, altering gene expression patterns that contribute to neoplastic transformation, tumorigenesis, and tumor behavior. This strain also contains the optimized form of reverse tetracycline controlled transactivator (rtTA-M2). Expression of Dnmt3b1 can be regulated with the tetracycline analog doxycycline (dox) in these double mutant offspring.When these mice are bred to C57BL/6J-ApcMin/J mice (see Stock No. 002020), DNMT3B1 expression in dox induced mice results an increase in intestinal tumor number and size as compared to ApcMin control mice.
Development
A targeting vector was designed to insert frt-flanked PGK-Neo-pA 500 bp downstream of the 3' UTR of the Col1a1 locus. This construct was electroporated into (C57BL/6 x 129S4Sv/Jae)F1-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were identified. One of these ES cells clones, C10, was retargeted to insert an optimized form of reverse tetracycline controlled transactivator (rtTA-M2) followed by a β-globin intron and polyA signal downstream of the Gt(ROSA)26Sor promoter. Correctly targeted ES cells were identified. One of these ES cell clones, KH2, was selected and the frt-flanked PGK-Neo-pA in the 3' UTR of the Col1a1 locus was replaced by co-injection of a tetO-Dnmt3b1 plasmid. The tetO-Dnmt3b1 plasmid contained a splice acceptor-double polyA sequence and the tetracycline responsive element (tetO) upstream of the DNA methyltransferase 3B gene.The resulting ES cells, now targeted with rtTA-M2 in the Gt(ROSA)26Sor locus (Rosa26-rtTA) and tetO-Dnmt3b1 in the Col1a1 locus (Col1a1-tetO-Dnmt3b1), were injected into recipient blastocysts. The donating investigator stated that the resulting chimeric mice were bred together and were subsequently backcrossed to C57BL/6J mice (see SNP note below) for at least 7 generations to establish the double mutant colony.
Upon arrival at The Jackson Laboratory Repository, these mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Col1a1
View Strains carrying other alleles of Col1a1 (13 strains)
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Caffey Disease (COL1A1)- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Collagen, Type I, Alpha-1; COL1A1 (COL1A1)
Ehlers-Danlos Syndrome, Type I (COL1A1)
Ehlers-Danlos Syndrome, Type VII, Autosomal Dominant (COL1A1)
Osteogenesis Imperfecta, Type I (COL1A1)
Osteogenesis Imperfecta, Type II (COL1A1)
Osteogenesis Imperfecta, Type III (COL1A1)
Osteogenesis Imperfecta, Type IV (COL1A1)
Osteoporosis (COL1A1)
Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 1; ICF1 (DNMT3B)
This mouse can be used to support research in many areas including:
Cancer Research
Genes Regulating Growth and Proliferation
Research Tools
Cancer Research
Tetop Tet System
Genetics Research
Mutagenesis and Transgenesis: Tetop Tet System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Col1a1tm9(tetO-Dnmt3b_i1)Jae | ||
|---|---|---|---|
| Allele Name | targeted mutation 9, Rudolf Jaenisch | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | tetO-Dnmt3b1; | ||
| Strain of Origin | (C57BL/6 x 129S4/SvJae)F1 | ||
| Expressed Gene | Dnmt3b, DNA methyltransferase 3B, mouse, laboratory | ||
| Expressed Gene | tetO, tet operator, | ||
| General Note | The allele was made in KH2 cells that carry Gt(ROSA)26Sortm1(rtTA*M2)Jae and Col1a1tm2(tetO-Pou5f1)Jae. | ||
| Molecular Note |
RMCE on KH2 cells inserted a cassette that contains a splice acceptor-double polyA sequence and the tetracycline responsive element (tetO) upstream of the DNA methyltransferase 3B gene isoform 1 ( | ||
| Gene Symbol and Name | Col1a1, collagen, type I, alpha 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | Col1a-1; Cola-1; Cola1; Moloney leukemia virus 13; Mov-13; OI4; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Col1a1tm9(tetO-Dnmt3b1)Jaealternate2 MCA,Separated MCA
Col1a1tm9(tetO-Dnmt3b1)Jae, Separated PCR
Col1a1tm9(tetO-Dnmt3b1)JaeMCA,Separated MCA
Col1a1tm9(tetO-Dnmt3b1)Jaealternate1, Separated PCR
Col1a1tm9(tetO-Dnmt3b1)Jaealternate2, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Linhart HG; Lin H; Yamada Y; Moran E; Steine EJ; Gokhale S; Lo G; Cantu E; Ehrich M; He T; Meissner A; Jaenisch R. 2007. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev 21(23):3110-22. [PubMed: 18056424] [MGI Ref ID J:127808]
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) 25-FEB-13 Diet Information LabDiet® 5K20
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Homozygous for Col1a1tm9(tetO-Dnmt3b*)Jae, Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae
Price per Pair (US dollars $) Pair Genotype $464.00 Homozygous for Col1a1tm9(tetO-Dnmt3b_i1)Jae, Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae x Homozygous for Col1a1tm9(tetO-Dnmt3b_i1)Jae, Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
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Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Homozygous for Col1a1tm9(tetO-Dnmt3b*)Jae, Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae
Price per Pair (US dollars $) Pair Genotype $603.20 Homozygous for Col1a1tm9(tetO-Dnmt3b_i1)Jae, Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae x Homozygous for Col1a1tm9(tetO-Dnmt3b_i1)Jae, Homozygous for Gt(ROSA)26Sortm1(rtTA*M2)Jae Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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