These mice carry a targeted knock-out allele of the mouse Pglyrp3 gene and are useful in studies of antibacterial immunity, inflammation, and microbiome in the gut and skin.
Roman Dziarski, Indiana University
Peptidoglycan recognition proteins (PGRPs), innate immunity proteins that are conserved from insects to mammals, recognize bacterial peptidoglycan, and function in antibacterial immunity. In mice, Pglyrp3 (peptidoglycan recognition protein 3) protects the colon from early inflammatory response and loss of the barrier function of intestinal epithelium by promoting normal bacterial flora and by preventing damaging production of interferon-γ by NK cells in response to injury. Pglyrp3 also protects mice from atopic dermatitis. Mammalian Pglyrp3 is directly bactericidal.
Exons 2 through 5 of the mouse Pglyrp3 gene were replaced with a neomycin cassette in this targeted knockout strain. Quantitative RT-PCR confirmed the absence of transcript expression in homozygotes.
Homozygotes are viable and fertile, and have no gross defects. They are, however, more sensitive than wild-type mice to dextran sulfate sodium (DSS)-induced colitis. This is due to a more inflammatory gut microflora, higher production of interferon-γ, higher expression of interferon-inducible genes, and an increase in NK cells causing hyperplasia of the lamina propria, loss of epithelium, and colon ulcers. Homozygotes are also more sensitive to oxazolone-induced atopic dermatitis due to a decrease in regulatory T cells (Treg) and an increase in Th17 cells.
Exons 2 through 5 of the mouse Pglyrp3 gene were replaced with a neomycin cassette via homologous recombination in 129S6/SvEvTac-derived iTL1 embryonic stem (ES) cells. This strain was backcrossed to BALB/cAnNHsd for 9 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize BALB/cByJ oocytes (Stock No. 001026).
In 2020, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as markers that distinguish between the substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. One of the 43 markers, on Chromosome 3, was segregating, likely a passenger segment for the targeted mutation. Also, one marker on Chromosome 7 was segregating between BALB/c substrains.
|Allele Name||targeted mutation 1, Roman Dziarski|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pglyrp3, peptidoglycan recognition protein 3|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exons 2 through 5 were replaced with a neo cassette. Quantitative RT-PCR confirmed the absence of transcript expression.|
Homozygotes and heterozygotes are viable and fertile.
When using the Pglyrp3- mouse strain in a publication, please cite the originating article(s) and include JAX stock #031371 in your Materials and Methods section.