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).
