Tlr7 Conditional Knockout mouse models

Tlr7 is the mouse ortholog of human TLR7 and encodes an endosomal receptor that requires UNC93B1 for trafficking and proteolytic maturation, then senses single-stranded RNA degradation products through two cooperating sites, one binding guanosine or synthetic agonists such as imiquimod and R848 and a second binding short uridine-containing oligoribonucleotides, with dimerization driving MyD88, IRAK4, and IRF7 dependent type I interferon in plasmacytoid dendritic cells. Dosage is central to disease logic: the Yaa locus duplication of Tlr7 accelerates murine lupus, human gain of function substitutions such as Y264H that increase guanosine affinity cause childhood systemic lupus erythematosus, and escape from X inactivation raises expression in females. Design accordingly, using conditional nulls to assign requirement to plasmacytoid dendritic cells or B cells, copy-number or point-mutant knockins for gain of function, and humanized alleles for agonist pharmacology. Tlr8 and Tlr9 overlap in nucleic acid sensing, so target autoantibody, interferon signature, or adjuvant endpoints.

A floxed Tlr7 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.