B6(Cg)-Zc3h12a^{tm1c(EUCOMM)Hmgu}/FumJ

Stock number: 032912
Product name: MCPIP1^fl
Strain synonyms: Mcpip1^flox
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Mcpip1^fl mice have loxP sites flanking exon 3 of the zinc finger CCCH type containing 12A (Zc3h12a) gene, making these mice useful for studying LPS-induced inflammation and lung injury.

Detailed description

Mcpip1^fl floxed mice have loxP sites flanking exon 3 of the zinc finger CCCH type containing 12A (Zc3h12a) gene. ZC3H12A (or MCPIP1) functions to regulate inflammatory cell activation and immune homeostasis. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues.

When bred to B6.129P2-Lyz2^tm1(cre)Ifo/J mice (Stock No. 004781), with Cre recombinase expression in cells of the myeloid lineage resulting mice exhibit no gross abnormalities until 5 months of age at which time they develop cachexia, splenomegaly, lymphadenopathy, multi-organ inflammation and premature death (60% live to 7 months of age). In addition, mice are sensitive to LPS-induced lung inflammation developing severe pulmonary inflammation and edema.

Development

The L1L2_gt2 cassette was inserted at position 125122864 of Chromosome 4 upstream of exon 3 (Build GRCm38). The cassette is composed of an FRT-flanked lacZ/neomycin sequence followed by a loxP site. An additional loxP site is inserted downstream of exon 3 at position 125121995. Thus, exon 3 is flanked by loxP sites. The construct was electroporated into C57BL/6N-derived JM8.N4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to B6.Cg-Tg(Pgk1-flpo)10Sykr/J (Stock No. 011065) to remove the lacZ-neomycin cassette. Mice were than bred to B6.129P2-Lyz2^tm1(cre)Ifo/J and maintained as heterozygous for both alleles. Mice were then crossed to C57BL/6 mice to remove the cre allele. Upon arrival, mice were bred to C57BL/6NJ (Stock 005304) for at least 1 generation to establish the colony.



In 2019 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 rederived living colony at The Jackson Laboratory Repository. While the 43 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Zc3h12a^{tm1c(EUCOMM)Hmgu}
Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
MGI accession ID: MGI:6115370
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Mcpip1^flox
Marker symbol: Zc3h12a
Marker name: zinc finger CCCH type containing 12A
Marker synonyms: dJ423B22.1; MCPIP; MCPIP1; MCPIP-1; MGC:41320; Reg1; Regnase-1; RGD1306776
Chromosome: 4
Strain of origin: C57BL/6N
Molecular note: The L1L2_gt2 cassette was inserted at position 125015788 of Chromosome 4 upstream of the critical exon(s) (Build GRCm39). The cassette is composed of an FRT flanked lacZ/neomycin sequence followed by a loxP site. An additional loxP site is inserted downstream of the targeted exon(s) at position 125016657. The critical exon(s) is/are thus flanked by loxP sites. A "conditional ready" (floxed) allele was created by flp recombinase expression in mice carrying this allele to remove the lacZ sequence and neo selection cassette, leaving loxP sites flanking the critical exon(s).