B6.129(Cg)-Mir122^tm1.2Kgh/J

Stock number: 036274
Product name: Mir122^loxP
Research areas: Cancer Research, Cell Biology Research, Research Tools

Description

Mir122^loxP mutant mice possess loxP sites flanking the Mir122 (microRNA 122) non-coding RNA and may be useful in generating conditional mutations to study liver homeostasis and hepatocellular carcinoma (HCC).

Detailed description

Mir122 (microRNA 122) encodes an abundant liver specific short, noncoding regulatory RNA that acts as negative regulator of gene expression by binding target mRNAs. Mir122 is involved in the regulation of serum cholesterol level, hepatitic C virus replication and suppression of tumorigenesis. These conditional Mir122^lox mice possess loxP sites flanking the Mir122 locus. Mice homozygous for the mutation are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have Mir122 deleted in cre-expressing tissues.

For example, when bred to mice with a liver specific Cre recombinase expression (such as Speer6-ps1^{Tg(Alb-cre)21Mgn}, Stock No. 003574) resulting offspring develop microsteatosis, and hepatitis in early adult life, and progressively develop fibrosis and spontaneous tumors resembling hepatocellular carcinoma (HCC) with age.

Development

The targeting construct was designed to insert loxP sites flanking the Mir122 sequence and the 569 bp flanking region followed by an FRT-flanked neomycin cassette. Mir122 is located on chromosome 18. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were crossed to C57BL/6 females and then crossed to an unspecified flp expressing mouse to remove the neomycin cassette. The strain was backcrossed to C57BL/6 for 6 generations by the donating laboratory (see SNP note below). Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

In 2021, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the male sent to The Jackson Laboratory Repository. One of the 43 markers throughout the genome was segregating with 129, on Chromosome 18, likely a passenger segment for the targeted mutation. Also, one of the 5 markers that determine C57BL/6J from C57BL/6N was found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Mir122^tm1.2Kgh
Name: targeted mutation 1.2, Kalpana Ghoshal
MGI accession ID: MGI:5448466
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Mir-122^fl; Mir122^loxP
Marker symbol: Mir122
Marker name: microRNA 122
Marker synonyms: hsa-mir-122; mir-122; MIR122A; Mir122b; MIRN122; Mirn122a; Mirn122b; miRNA122; miRNA122A; mmu-mir-122; mmu-mir-122a
Chromosome: 18
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: The microRNA sequence was floxed and an FRT-flanked neo cassette was inserted downstream of the floxed sequence. Flp-mediated recombination removed the FRT-flanked neo cassette.