Tbk1 Conditional Knockout mouse models

Tbk1, the mouse ortholog of human TBK1, encodes a serine threonine kinase of the IKK family with kinase, ubiquitin-like, and scaffold dimerization domains that phosphorylates STING at Ser366 and IRF3 at Ser396 to drive type I interferon transcription downstream of cGAS, RIG-I through MAVS, and TLR3 through TRIF, and separately phosphorylates the autophagy receptors OPTN and SQSTM1 to license selective mitophagy and xenophagy. Human haploinsufficiency and loss of function mutations cause amyotrophic lateral sclerosis and frontotemporal dementia, while excess interferon output underlies its interest in autoinflammation. Germline nulls die at midgestation from TNF-dependent hepatic apoptosis, a lethality rescued on a Tnfrsf1a-null background, so practical alleles include kinase-dead knockins, phosphosite mutants, conditional deletion, and truncating patient variants. Ikbke partially covers interferon induction in myeloid cells, so compound genetics may be required, and allele choice should track interferon output, mitophagy flux, or motor neuron phenotypes.

Tbk1 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.