LacZ expression of the Aim2/LacZ fusion protein in macrophages and splenocytes of these mice replaces the endogenous expression of the absent in melanoma 2 gene (Aim2). These mice may be useful for studying the innate immune system's response to bacterial and viral infection. Aim2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death, and may be a therapeutic target for ionizing radiation exposure.
Katherine A Fitzgerald, University of Massachusetts Medical Scho
This secretory trap mutation abolishes Aim2 (endogenous absent in melanoma 2) gene function while expressing an Aim2/LacZ/neo (β-geo) fusion protein. AIM2 is a proinflammatory protein which is a critical part of the inflammasome. LacZ is expressed from the targeted allele in thioglycolate-elicited macrophages (TEMs), bone marrow-derived macrophages (BMDMs), and splenocytes. Homozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These Aim2-/- mice may be useful as a lacZ reporter for AIM2 expression or as a knockout model for studying the innate immune systems response to bacterial and viral infection.
New findings (November, 2016) show that mice deficient in the double-stranded DNA sensor Aim2 are protected from both subtotal body irradiation–induced gastrointestinal syndrome and total body irradiation–induced hematopoietic failure. Mechanistically, it has been found that Aim2 senses radiation-induced DNA damage in the nucleus to mediate inflammasome activation and cell death. The gene may be a new therapeutic target for ionizing radiation exposure.
A "secretory trap" targeting vector was used replace the C-terminus of the endogenous absent in melanoma 2 (Aim2) targeted gene with a β-geo fusion protein. This gene trap targeting vector integrated randomly into the Aim2 locus via electroporation into 129P2/OlaHsd-derived E14TG2a.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric mice were bred with C57BL/6 mice to establish the mutant colony. Upon arrival at The Jackson Laboratory, mice were backcrossed to C57BL/6J (Stock No. 000664) for at least 7 more generations to establish a congenic colony.
|Allele Name||gene trap CSG445, BayGenomics|
|Allele Type||Gene trapped (Reporter, Null/Knockout)|
|Gene Symbol and Name||Aim2, absent in melanoma 2|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||The beta-geo containing gene trap vector inserted into intron 6. The absence of protein expression was confirmed by western blot analysis on thioglycollate-elicited and bone marrow-derived macrophage extracts.|
When maintaining a live colony, homozygous mice may be bred together.
When using the Aim2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #013144 in your Materials and Methods section.