Tlr3 Conditional Knockout mouse models

Tlr3, the mouse ortholog of human TLR3, encodes the endosomal receptor for double-stranded RNA, binding duplexes of roughly forty five base pairs or longer across two sites on the lateral face of its leucine-rich repeat ectodomain so that two receptors are bridged into a signaling dimer, with acidic pH and UNC93B1-dependent trafficking required for function. Uniquely among Toll-like receptors it signals exclusively through TRIF rather than MyD88, recruiting TRAF3, TBK1, and IKK epsilon to phosphorylate IRF3 for type I interferon and, through RIPK1, driving NF-kB or RHIM-dependent death, and human TLR3 deficiency predisposes specifically to herpes simplex encephalitis. Nulls are viable and immunocompetent outside particular viral challenges, so germline deletion is practical, while conditional alleles resolve neuronal, epithelial, and dendritic cell sensing and humanized ectodomains matter for agonist pharmacology. Since Ddx58 and Ifih1 also sense duplex RNA in cytosol, plan compound genetics around interferon induction or neurotropic infection endpoints.

A floxed Tlr3 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.