Aim2 Conditional Knockout mouse models

Aim2, the mouse ortholog of human AIM2, encodes an interferon-inducible HIN-200 family sensor that pairs an N-terminal pyrin domain with a C-terminal HIN200 domain gripping the sugar-phosphate backbone of cytosolic double-stranded DNA in sequence-independent fashion. DNA binding relieves intramolecular autoinhibition, allowing pyrin domain filaments to nucleate ASC (Pycard) into a caspase-1 activating platform that matures pro-IL-1beta and pro-IL-18 and cleaves gasdermin D to drive pyroptosis, the core response to Francisella, cytomegalovirus, and self DNA released after genotoxic stress. Conditional nulls isolate cell-intrinsic sensing in macrophages, dendritic cells, or intestinal epithelium, whereas HIN200 point mutants that abolish DNA binding without removing protein separate sensing from scaffolding, and humanization supports inhibitor programs. Bear in mind the murine Ifi200 cluster contains Ifi202b, Ifi203, and Ifi204, which share HIN domains and can obscure phenotypes, while parallel Nlrp3 and Nlrc4 inflammasomes provide overlapping IL-1beta output, so pairing an allele with the right myeloid Cre and cytokine endpoint is essential.

A floxed Aim2 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.