LRG-47 knock-out mice exhibit reduced macrophage responses and increased susceptibility to infection by Toxoplasmsma gondii, Lysteria monocytogenes, Salmonella typhimurium, and murine cytomegalovirus (MCMV), and may be useful for the study of immunology and infectious disease.
Dr. Gregory A Taylor, Duke University
Immunity-related GTPase family M member 1 (Irgm1) is a member of the Immunity Related GTPase (IRG) family of genes which encode 47-48kD GTP-binding proteins transcriptionally upregulated by the activation of interferon gamma. Mice homozygous for the deletion of Irgm1 (also known as LRG-47 KO mice) have normal expression of myeloid and lymphoid cell populations, but show reduced macrophage activation and increased susceptibility to infection by the protozoan Toxoplasmsma gondii (100% mortality by 12 days post administration), as well as many bacteria including Listeria monocytogenes (100% mortality by 5 days post administration) (Collazo et al. 2001) and Salmonella typhimurium (Henry et al. 2007).
Important Note: The donating investigator indicates that, in their facility, homozygous LRG-47 mice have no overt abnormal phenotypes and are not significantly different in bodyweight from their wildtype counterparts. However, heterozygous X heterozygous matings produce fewer than the expected Mendelian ratio of homozygotes and surviving homozygotes are poor breeders on congenic C57BL/6NJ, 129S1/SvImJ, and mixed B6;129 backgrounds. Similarly, it is the experience of The Jackson Laboratory that when breeding heterozygous X heterozygous, very few homozygotes are produced and those that survive are runted and unsuitable for breeding.
The Irgm1tm1Gat allele was created in the laboratory of Dr. Gregory A. Taylor at Duke University. A targeting vector was constructed to replace 0.7kb of the coding region of the immunity-related GTPase family M member 1 (Irgm1) gene with a PGK-neoBpA cassette. The construct was electroporated into 129/Sv-derived CJ7 ES cells and then microinjected into recipient blastocysts. The chimeric animals were crossed to C57BL/6NCrl mice for germline transmission and the line was subsequently backcrossed 8 generations to C57BL/6NCrl prior to being donated to The Jackson Laboratory in 2020. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).
|Allele Name||targeted mutation 1, Gregory A Taylor|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Irgm1; LRG-47-|
|Gene Symbol and Name||Irgm1, immunity-related GTPase family M member 1|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||5 kb of genomic sequence were replaced with a neomycin selection cassette inserted by homologous recombination. Included in the deleted region was 0.7 kb of protein coding region. Western blot analysis of MEFs indicated an absence of protein in homozygous mutant mice.|
Heterozygous mice are viable and fertile, with no reported gross phenotypic or behavioral abnormalities.
When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304).
Note: The donating investigator indicates that in their facility, heterozygous X heterozygous matings produce fewer than the expected Mendelian ratio of homozygotes and surviving homozygotes are poor breeders on congenic C57BL/6NJ, 129S1/SvImJ, and mixed B6;129 backgrounds. Similarly, it is the experience of The Jackson Laboratory that when breeding heterozygous X heterozygous, very few homozygotes are produced and those that survive are runted and unsuitable for breeding.
When using the LRG-47 KO
mouse strain in a publication, please cite the originating article(s) and include JAX stock #034643 in your Materials and Methods section.