Rhbdf2 (rhomboid 5 homolog 2) knock-out produce little TNFα in response to LPS administration or infection with L. monocytogenes. These mice may be useful for studies of regulation of innate immunity, sepsis and TNFα-mediated disease.
Dr. Tak Mak, University Health Network/Un of Toronto
Rhbdf2 (rhomboid 5 homolog 2) is a member of the rhomboid family of intramembrane serine proteases and is involved in regulating the secretion of tumor necrosis factor alpha (TNFα). Mice homozygous for this knock-out allele are viable and fertile. Following administration of lipopolysaccharide (LPS), KO mice produce substantially less serum TNFα than controls and are resistant to a lethal LPS dose. Infection of KO mice with L. monocytogenes results in only small amounts of serum TNFα, although production of IL6, IL12 and IFNΓ are not affected. Infected KO mice develop increased granulomas, high bacterial titers and rapidly succumb to infection. These mice may be useful for studies of regulation of innate immunity, sepsis and TNFα-mediated disease.
The targeting vector used a neomycin cassette, in reverse orientation, to replace exons 4 to 14. The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J to achieve germline transmission. The mice were then backcrossed to C57BL/6 for 9 generations. Upon arrival, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm is used to fertilize C57BL/6J.
|Allele Name||targeted mutation 1, Tak Mak|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||iR2-; iRhom2-|
|Gene Symbol and Name||Rhbdf2, rhomboid 5 homolog 2|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 2.5 kb genomic fragment containing exons 4-14 was replaced with a pgk-neo cassette via homologous recombination.|
When maintaining a live colony, these mice are bred by homozygote sibling matings.
When using the iRhom2- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #44040 in your Materials and Methods section.
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