Mice homozygous for this "knockout" allele of the Plac8 (placenta-specific 8 or Onzin) locus exhibit impaired host defense compared to wild-type mice. Because high expression of Onzin is normally observed in intestinal tract epithelial cells, lung epithelial cells, and immune system cells (including macrophages and granulocytes), these mutant mice may be useful in studying the role of Onzin in host defense and innate immune function (such as bacterial uptake in neutrophils).
Beverly H Koller, University of North Carolina at Chapel Hill
Homozygous (Onzin-/-) mice are viable and fertile with a loxP-flanked pgk-neo cassette disrupting exon 4 of the Plac8 (placenta-specific 8 or Onzin) locus. Tissues from homozygous mice have no RNA (full-length/isoforms/altered splice variants) or protein expression from the targeted allele. Histological and peripheral blood analysis of homozygous mice is indistinguishable from wild-type mice. Similarly, leukocyte populations in the thymus, spleen, and lymph nodes exhibit no gross changes in the development of T cell, B cell, or macrophage populations associated with Onzin-deficiency. Compared to wild-type mice, Onzin-deficient mice exhibit impaired host defense; when given intraperitoneal injection of Klebsiella pneumonia, homozygotes develop acute peritonitis and heightened innate immune response consistent with an increased bacterial burden. Neutrophils isolated from homozygous mice exhibit normal phagocytosis but less effective killing of bacteria. Because high expression of Onzin is normally observed in intestinal tract epithelial cells, lung epithelial cells, and immune system cells (including macrophages and granulocytes), these mutant mice may be useful in studying the role of Onzin in host defense and innate immune function (such as bacterial uptake in neutrophils).
A targeting construct was designed to replace a 330 bp region (including the 5' end of exon 4) of the Onzin (Plac8) locus with a loxP-flanked pgk-neo cassette. The donating investigator reports that this construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with 129S6/SvEvTac mice to generate the mutant colony. Mutant mice were subsequently backcrossed to C57BL/6J for at least 15 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.
|Allele Name||targeted mutation 1, Beverly H Koller|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Plac8, placenta-specific 8|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A portion of intron 3 and exon 4 was replaced with a floxed neo cassette. The absence of protein expression was confirmed by western blot analysis on intestine, spleen, and neutrophil extracts.|
|Mutations Made By|| |
Beverly Koller, University of North Carolina at Chapel Hill
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129S6-Plac8tm1Bhk/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009598 in your Materials and Methods section.