B6.129-Mirc14^tm1.1Czc/J

Stock number: 025872
Research areas: Cancer Research, Cell Biology Research, Research Tools

Description

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.

Detailed description

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)26Sor^{tm1(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).

Development

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

Symbol: Mirc14^tm1.1Czc
Name: targeted mutation 1.1, Chang-Zheng Chen
MGI accession ID: MGI:5467776
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Mirc14
Marker name: microRNA cluster 14, including Mir181a-1 through Mir181b-1
Chromosome: 1
Strain of origin: 129P2/OlaHsd
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.