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| Col1a1-tetO-OKSM mice have expression of the OKSM cassette (four mouse reprogramming genes Oct4 [Pou5f1], Klf4, Sox2, and c-Myc [Myc]) under the control of the bi-directional tet-responsive element (tetO; also called tetracycline operator, tet-operator, or tetracycline-responsive element [TRE]) with CMV minimal enhancer-less promoter. When bred with another mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), expression of the OKSM cassette can be regulated with the tetracycline analog doxycycline (dox) in the resulting double mutant offspring. Somatic expression of the OKSM reprogramming factors allows multiple somatic cell types to be directly reprogrammed to generate induced pluripotent stem cells (iPSCs). | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
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- References
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Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 26-APR-12 Species laboratory mouse Generation F?
Generation DefinitionsDonating Investigator Konrad Hochedlinger, Massachusetts General Hospital / Harvard Description
Mice homozygous for the Col1a1-tetO-OKSM targeted mutation are viable and fertile, although the donating investigator reports that homozygous mice do not breed as well as expected. Expression of the OKSM cassette (four mouse reprogramming genes Oct4 [Pou5f1], Klf4, Sox2, and c-Myc [Myc]) is controlled by the tet-responsive element (tetO; also called tetracycline operator, tet-operator, or tetracycline-responsive element [TRE]) with CMV minimal enhancer-less promoter. When bred with another mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA), expression of the OKSM cassette can be regulated with the tetracycline analog doxycycline (dox) in the resulting double mutant offspring. Somatic expression of the OKSM reprogramming factors allows multiple somatic cell types to be directly reprogrammed to generate induced pluripotent stem cells (iPSCs). Because the reprogramming factors are carried on a single polycistronic construct, these Col1a1-tetO-OKSM mice can be easily maintained and the transgene can be easily transferred into other genetic backgrounds if needed.Specifically, breeding Col1a1-tetO-OKSM mice with R26-rtTA mice (see Stock No. 006965) results in double mutant mice called Collagen-OKSM. Collagen-OKSM mouse embryonic fibroblasts (MEFs) cultured in dox for 8-12 days give rise to iPSC colonies that can be propagated in the absence of dox. A wide variety of somatic cell types can be reprogrammed using the Collagen-OKSM system; with reprogramming of hematopoietic stem and progenitor being especially efficient. The Collagen-OKSM genotype, cell types (and reported reprogramming frequency) are listed below. When heterozygous for both the Rosa26-rtTA and Col1a1-tetO-OKSM mutations, hematopoietic stem cells (5-10%), granulocyte-macrophage progenitors (5-10%), mouse embryonic fibroblasts (1-2%), postnatal tail-tip fibroblasts (0.2%), and monocytes (0.1%) may be used to generate iPSCs. When homozygous for the Rosa26-rtTA mutation and heterozygous for the Col1a1-tetO-OKSM mutation, hematopoietic stem cells (up to 40%), granulocyte-macrophage progenitors (15-20%), postnatal tail-tip fibroblasts (1%), monocytes (0.3%), T cells (<0.05%), granulocytes (<0.05%), and B cells (<0.05%) may be used to generate iPSCs. Collagen-OKSM chimeras derived from reprogrammed cells (homozygous for the Rosa26-rtTA mutation and heterozygous for the Col1a1-tetO-OKSM mutation) have ~80% incidence of an aggressively growing tumor that histologically presents as a largely undifferentiated teratoma by three months of age. In contrast, incidence is reduced to ~30% by three months of age when heterozygous for both mutations.
Development
A targeting vector was designed to insert frt-flanked PGK-Neo-pA into 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 tetOP-OKSM "flip-in plasmid" and a CAG-Flpe plasmid. The tetOP-OKSM "flip-in plasmid" contained a splice acceptor-double polyA sequence and the tetracycline responsive element (TRE, tetOP, or tetO) upstream of the four mouse reprogramming genes Oct4 (Pou5f1; POU domain, class 5, transcription factor 1), Klf4 (Kruppel-like factor 4 (gut)), Sox2 (SRY-box containing gene 2), and c-Myc (Myc; myelocytomatosis oncogene). An internal ribosome entry site (IRES) sequence was placed between the coding sequences for Klf4 and Sox2. Expression of Pou5f1/ Klf4 and Sox2/Myc was linked by self-cleaving peptides that mediate ribosomal skipping (F2A [from foot-and-mouth disease virus] and E2A [from equine rhinitis A virus], respectively).
The resulting ES cells, now targeted with rtTA-M2 in the Gt(ROSA)26Sor locus (Rosa26-rtTA) and tetOP-OKSM in the Col1a1 locus (Col1a1-tetO-OKSM), were injected into recipient blastocysts. Chimeric mice were bred together to establish the double mutant colony. Double mutant mice were bred together, and some of the animals were chosen with the Col1a1-tetO-OKSM mutation and without the Rosa26-rtTA mutation. At some point, Oct4-GFP mutant mice (on the same C57BL/6;129S4Sv/Jae mixed genetic background; see Stock No. 008214) were bred to these mice as well, but the Oct4-GFP mutation was later bred away.
Mice harboring only the Col1a1-tetO-OKSM mutation (on a C57BL/6;129S4Sv/Jae mixed genetic background) were sent to The Jackson Laboratory Repository. Upon arrival, Col1a1-tetO-OKSM mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Col1a1
View Strains carrying other alleles of Col1a1 (13 strains)
Additional Web Information
Tet Expression Systems
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)
Burkitt Lymphoma; BL (MYC)
Microphthalmia, Syndromic 3; MCOPS3 (SOX2)
assigned by genotype
Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch/Col1a1+
involves: 129S4/SvJae * C57BL/6
- no phenotypic analysis
- *normal* no phenotypic analysis (MGI Ref ID J:159350)
This mouse can be used to support research in many areas including:
Cancer Research
Other
Cell Biology Research
Transcriptional Regulation
Research Tools
Cancer Research
Tetop Tet System
genes regulating teratoma development
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Tetop Tet System
Mutagenesis and Transgenesis: transcriptional activation
Tet Expression Systems
tTA/rtTA Responsive Strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Konrad Hochedlinger | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Col1a1-tetO-OKSM; | ||
| Mutation Made By | Konrad Hochedlinger, Massachusetts General Hospital / Harvard | ||
| Strain of Origin | (C57BL/6 x 129S4/SvJae)F1 | ||
| Expressed Gene | tetO, tet operator, | ||
| Expressed Gene | Sox2, SRY-box containing gene 2, mouse, laboratory | ||
| Expressed Gene | Klf4, Kruppel-like factor 4 (gut), mouse, laboratory | ||
| Expressed Gene | Pou5f1, POU domain, class 5, transcription factor 1, mouse, laboratory | ||
| Expressed Gene | Myc, myelocytomatosis oncogene, mouse, laboratory | ||
| General Note | The allele was made in KH2 cells that carry Gt(ROSA)26Sortm1(rtTA*M2)Jae and Col1a1tm2(tetO-Pou5f1)Jae. | ||
| Molecular Note | A targeting vector was designed to insert frt-flanked PGK-Neo-pA into 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 beta-globin intron and polyA signal downstream of the Gt(ROSA)26Sor promoter. Correctly targeted ES cellswere 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 tetOP-OKSM "flip-in plasmid" and a CAG-Flpe plasmid. The tetOP-OKSM "flip-in plasmid" contained a splice acceptor-double polyA sequence and the tetracycline responsive element (TRE, tetOP, or tetO) upstream of the four mouse reprogramming genes Oct4 (Pou5f1; POU domain, class 5, transcription factor 1), Klf4 (Kruppel-like factor 4 (gut)), Sox2 (SRY-box containing gene 2), and c-Myc (Myc; myelocytomatosis oncogene) separated by three different sequences that mediate ribosomal skipping (F2A [from foot-and-mouth disease virus], IRES [internal ribosome entry site], and E2A [from equine rhinitis A virus], respectively). The resulting ES cells, now targeted with rtTA-M2 in the Gt(ROSA)26Sor locus (Rosa26-rtTA) and tetOP-OKSM in the Col1a1 locus (Col1a1-tetO-OKSM), were injected into recipient blastocysts. Chimeric mice were bred together to establishthe double mutant colony. Double mutant mice were bred together, and some of the animals were chosen with the Col1a1-tetO-OKSM mutation and without the Rosa26-rtTA mutation. [MGI Ref ID J:159350] | ||
| Gene Symbol and Name | Col1a1, collagen, type I, alpha 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | COLIA1; Col1a-1; Cola-1; Cola1; Moloney leukemia virus 13; Mov-13; OI4; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Col1a1 3'UTR assay2 (flip-in), Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Stadtfeld M; Maherali N; Borkent M; Hochedlinger K. 2010. A reprogrammable mouse strain from gene-targeted embryonic stem cells. Nat Methods 7(1):53-5. [PubMed: 20010832] [MGI Ref ID J:159350]
Additional References
Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch relatedWesemann DR; Portuguese AJ; Magee JM; Gallagher MP; Zhou X; Panchakshari RA; Alt FW. 2012. Reprogramming IgH isotype-switched B cells to functional-grade induced pluripotent stem cells. Proc Natl Acad Sci U S A 109(34):13745-50. [PubMed: 22869756] [MGI Ref ID J:188595]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX18
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred with wildtype mice from the colony. If homozygous mice are bred together, the donating investigator reports that homozygous mice do not breed as well as expected. Mating System Homozygote x Homozygote (Female x Male) 26-APR-12 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Homozygous for Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch
Price per Pair (US dollars $) Pair Genotype $464.00 Homozygous for Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch x Homozygous for Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along 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. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Homozygous for Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch
Price per Pair (US dollars $) Pair Genotype $603.20 Homozygous for Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch x Homozygous for Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along 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. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
|
|
|
Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along 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. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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