In this conditional mutation strain, microRNA mir-181ab1 (Mir181a-1-Mir181b-1; also called Mirc14) is flanked by loxP sites. Cre excision of the floxed region enables tissue/cell-specific knockouts of the genes. Germline deletion reveals that Mir181a-1-Mir181b-1 controls the development of normal thymic T cells and inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). These are potential targets for inhibiting tumor development that evoke little toxicity to normal development.
Chang-Zheng (Eric) Chen, Achelois Pharmaceuticals, Inc.
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), No functional change) | Mirc14 | microRNA cluster 14, including Mir181a-1 through Mir181b-1 |
MicroRNAs are an abundant class of small regulatory RNAs that control gene expression at the posttranscriptional level. Some are integral components of oncogenic and tumor suppressing networks that make ideal targets for inhibiting tumor development with little toxicity to normal development.
The miR-181 family of genes (mir-181ab1 (Mir181a-1 - Mir181b-1; also called Mirc14), mir-181ab2 (Mir181a-2 - Mir181b-2; also called Mirc15) and mir-181cd (Mir181c - Mir181d; also called Mirc16)) produce four nearly identical mature miRNAs (miR-181a, miR-181b, miR-181c and miR-181d) from polycistronic transcripts. MiR181a miRNAs are highly expressed in T cell acute lymphoblastic leukemia (T-ALL) cells and down-regulated during remission.
In this conditional mutation strain, mir-181ab1 (Mirc14) is flanked by loxP sites. Cre excision of the floxed region enables tissue/cell-specific knockouts of the genes.
For example, when bred to B6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J (Stock No. 008463), tamoxifen-induced Cre-mediated recombination results in altered development of normal thymic T cells and leukemia cells.
Germline deletion reveals that Mir181a-1-Mir181b-1 controls the development of normal thymic T cells and inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL).
A loxP-Mir181a-1 - Mir181b-1-FRT-PGK-neomycin-FRT-loxP targeting construct was introduced to CGR8 129P2/OlaHsd-derived embryonic stem cells. The FRT-flanked PGK-neomycin cassette was excised through crosses with a 129S4 background Gt(ROSA)26Sor Flp recombinase strain (see Stock No. 007844). Mice were backcrossed to C57BL/6J for 10 generations by the donating laboratory.
Allele Name | targeted mutation 1.1, Chang-Zheng Chen |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | mir181a1b1f |
Gene Symbol and Name | Mirc14, microRNA cluster 14, including Mir181a-1 through Mir181b-1 |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 1 |
Molecular Note | LoxP sites were inserted at least 125 bp upstream and downstream of the cluster. Flp-mediated recombination removed an FRT-flanked neo cassette. |
Homozygous floxed mice are viable and fertile.
When using the B6.129-Mirc14tm1.1Czc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025872 in your Materials and Methods section.
Facility Barrier Level Descriptions
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Heterozygous for Mirc14<tm1.1Czc> |
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