B6.129S-Mirc30^tm1.1Rdf/J

Stock number: 017641
Product name: miR-15a/16-1 fl
Research areas: Cancer Research, Research Tools

Description

These floxed mutant mice possess loxP sites flanking the Mir15a/Mir16-1 cluster. This strain may be useful for generating conditional mutations in applications related to tumorigenesis and therapeutic management of chronic lymphocytic leukemia.

Detailed description

The Mir15a/Mir16-1 cluster, located in the human 13q14 chromosomal region (conserved in mouse 14qC3), is involved in regulation of B cell proliferation. When deleted, B cell proliferation is accelerated. Chromosomal deletion of human 13q14 is commonly associated with poor prognosis in chronic lymphocytic leukemia (CLL). These mice possess loxP sites on either side of the Mir15a/Mir16-1 cluster. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have Mir15a/Mir16-1 cluster deleted in the cre-expressing tissue(s).

When bred to a strain with Cre recombinase expression in B lymphocytes (see Stock No. 006785 for example), this mutant mouse strain may be useful in studies of chronic lymphocytic leukemia.

Development

A targeting vector containing an FRT flanked MC1-NEO cassette was used to insert a loxP site centromeric the Mir15a/Mir16-1 cluster. A second loxP site was inserted between the Mir15a/Mir16-1 cluster and exon 4 of the Dleu2 gene. The construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were crossed to a FLP recombinase expressing transgenic strain (Stock No. 003946) to remove the selection cassette and then backcrossed to C57BL/6 for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Mirc30^tm1.1Rdf
Name: targeted mutation 1.1, Riccardo Dalla-Favera
MGI accession ID: MGI:4437043
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Mirc30
Marker name: microRNA cluster 30, including Mir16-1 through Mir15a
Chromosome: 14
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Molecular note: The locus was floxed and an FRT flanked neo cassette was inserted centromeric to the locus by homologous recombination. The selection cassette was removed by flp mediated recombination. RT-PCR confirmed normal expression of the micro RNAs and Dleu2.