STOCK Mir34a^tm1.2Aven/J

Stock number: 018545
Product name: miR-34a^fl
Research areas: Apoptosis Research, Cancer Research, Cell Biology Research, Neurobiology Research, Research Tools

Description

Conditional miR-34a^fl/fl floxed mutant mice may have applications in studies related to the regulatory control of p53 pathways.

Detailed description

The miR-34 family of miRNAs (miR-34a, miR-34b, and miR-34c) are expressed mainly in the testis, brain, and lung. miR-34 proteins are induced upon p53 activation and are associated with tumor suppression, aging, neurodegeneration, and spermatogenesis. miR-34a^fl/fl mice possess loxP sites flanking the entire microRNA 34a (miR-34a) sequence. Homozygous miR-34a^fl/fl mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have miR-34a sequence deleted in the cre-expressing tissues. When crossed to mice expressing CAG-cre, miR-34a^-/- mice exhibit abnormal neuronal precursor proliferation. When cre recombined miR-34a^-/- mice are bred to Mirc21^-/- mice (Stock No. 018546), which are deficient in miR-34b and miR-34c, the double mutant mice lack all three miR-34 family members. These miR-34 KO mice show normal development with an intact p53 pathway.

Development

A targeting vector was designed to insert a loxP site upstream of the pre- microRNA 34a (miR-34a) sequence, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of the pre-miR-34a sequence. The construct was electroporated into (C57BL/6 x 129S4/SvJae)F1-derived V6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to Tg(ACTFLPe)9205Dym transgenic mice on a B6 background to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, resulting in a colony of miR-34a^fl/fl mice. These mice were maintained on mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Mir34a^tm1.2Aven
Name: targeted mutation 1.2, Andrea Ventura
MGI accession ID: MGI:5320795
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Mir34a
Marker name: microRNA 34a
Chromosome: 4
Strain of origin: (C57BL/6 x 129S4/SvJae)F1
Molecular note: A targeting vector was designed to insert a loxP site upstream of the sequence, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, downstream of the sequence. Flp-mediated recombination removed the neo cassette and left the sequence floxed.