These mice express Let-7S21L (let-7g (Mirlet7g) Stem, mir-21 (Mir21) Loop) under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter and are useful in studies of growth and metabolism.
George Q. Daley, Children's Hospital Boston
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Inducible, Inserted expressed sequence, RMCE-ready) | Col1a1 | collagen, type I, alpha 1 |
Lin28a (lin-28 homolog A (C. elegans)) and Lin28b (lin-28 homolog B (C. elegans)) encode RNA-binding proteins that block the biogenesis of Mirlet7 (let-7) microRNAs. Let-7 targets are known regulators of mammalian body size and metabolism.
This strain was constructed to determine whether altered let-7 expression might produce phenotypes opposite those of strains over-expressing Lin28a (see Stock No. 023910) or Lin28b (see Stock No. 0023911). It expresses Let-7S21L (let-7g Stem, mir-21 Loop) under the regulatory control of a Col1a1 (collagen, type I, alpha 1)-driven tetO promoter. Let-7S21L represents a chimeric Mirlet7g (microRNA let7g) stem/Mir21 (microRNA 21) loop fusion that cannot bind LIN28, thus allowing for let-7 processing despite Lin28 expression. This ensures that endogenous LIN28 cannot block pri- or pre-let-7g biosynthesis.
Mirlet7g/Mir21 expression can be regulated in progeny derived from crosses with rtTA or tTA mice. When crossed with Gt(ROSA)26Sor M2-rtTA strain (see Stock No. 006965), uninduced male mice exhibit no leakiness of expression and exhibit no growth or glucose phenotypes. Widespread induction from three weeks of age onward increases mature MIRLET7G levels in liver (>50-fold), skin (>20-fold), fat (approximately 4-fold) and muscle (approximately 4-fold). Induced animals show reduced body size and growth rates. After 5 days of induction, mice produce an increase in fed state glucose. Glucose tolerance testing reveals glucose intolerance in mice fed either a normal or high fat diet. Insulin tolerance testing fails to detect a difference in insulin sensitivity. Mutant mice produce more insulin than control mice.
A targeting vector containing a splice acceptor, 2 polyadenylation sequences, a tetracycline operator, let-7S21L, and an SV40 polyadenylation signal within 3'UTR of the mouse Col1a1 gene was introduced to (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells containing M2-rtTA (optimized rtTA) targeted to the Gt(ROSA)26Sor locus promoter (see Stock No. 006965 for mutation details). Let-7S21L (let-7g Stem, mir-21 Loop) represents a chimeric Mirlet7g (microRNA let7g) stem/Mir21 (microRNA 21) loop fusion. Resultant chimeric males were crossed with outbred CD1 females. The Gt(ROSA)26Sor M2-rtTA mutation was bred away from this strain. The line was backcrossed to C57BL/6 for 8 generations by the donating lab.
Allele Name | targeted mutation 3, George Q Daley |
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Allele Type | Targeted (Inducible, Inserted expressed sequence, RMCE-ready) |
Allele Synonym(s) | iLet-7; let-7; let-7S21L |
Gene Symbol and Name | Col1a1, collagen, type I, alpha 1 |
Gene Synonym(s) | |
Promoter | tetO, tet operator, |
Strain of Origin | (C57BL/6 x 129S4/SvJae)F1 |
Chromosome | 11 |
General Note | The allele was made in KH2 cells that carry Gt(ROSA)26Sortm1(rtTA*M2)Jae and Col1a1tm13(neo/hygro*)Jae (J:159351). This allele was generated with Col1a1tm13(neo/hygro*)Jae. |
Molecular Note | RMCE on KH2 cells inserted a cassette that contains a splice acceptor, 2 polyadenylation sequence, tetracycline operator, a fusion of the Mirlet7g stem sequence and the Mir21 loop sequence, and an SV40 polyadenylation signal into the 3'UTR. No expression of the inserted sequence is detected in the absence of doxycycline treatment. |
Homozygous and heterozygous mice are viable and fertile.
When using the B6.Cg-Col1a1tm3(tetO-Mirlet7g/Mir21)Gqda/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023912 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Col1a1<tm3(tetO-Mirlet7g/Mir21)Gqda> |
Frozen Mouse Embryo | B6.Cg-Col1a1<tm3(tetO-Mirlet7g/Mir21)Gqda>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Col1a1<tm3(tetO-Mirlet7g/Mir21)Gqda>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Col1a1<tm3(tetO-Mirlet7g/Mir21)Gqda>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.Cg-Col1a1<tm3(tetO-Mirlet7g/Mir21)Gqda>/J Frozen Embryo | $3373.50 |
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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. 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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