Mouse TIR-deleted TLR Genes

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pZERO-mTLR1tirless

InvivoGen

Catalog Number: pzero-mtlr1
Description: TLR1, the first member of the toll-like receptor family, was identified by the presence of a domain homology found in both Drosophila Toll and human interleukin-1 receptors. TLR1 is expressed at higher levels in the spleen and peripheral blood cells. No direct ligands have been identified so far for TLR1, and its function remains unclear. TLR1 seems to act as a coreceptor. TLR1 was shown to associate with TLR2 in response to triacylated lipopeptides, but not diacylated lipopeptides. These observations suggest that TLR1 is able to discriminate among lipoproteins by recognizing the lipid configuration. TLR1-?TIR is a TIR-less form of the TLR1 gene generated by deleting the TIR domain (453 bp).

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pZERO-mTLR2tirless

InvivoGen

Catalog Number: pzero-mtlr2
Description: TLR2 is involved in the recognition of multiple products of Gram-positive bacteria, mycobacteria and yeast. TLR2 has been shown to confer responsiveness to the lipopeptides present in LPS preparations. However, it seems that some types of LPS can activate TLR2. TLR2 is known to heterodimerize with other TLRs, a property believed to extend the range of PAMPs that TLR2 can recognize. TLR2 cooperates with TLR6 in the response to peptidoglycan and diacylated mycoplasmal lipopeptide, and associates with TLR1 to recognize triacylated lipopetides. Furthermore, pathogen recognition by TLR2 is strongly enhanced by CD14.TLR2-?TIR is a TIR-less form of the TLR2 gene generated by deleting the TIR domain (429 bp). This truncated gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR3tirless

InvivoGen

Catalog Number: pzero-mtlr3
Description: TLR3 recognizes double-stranded RNA (dsRNA), a molecular pattern associated with viral infection. Stimulation with polyinosine-polycytidylic acid (poly(I:C)), a synthetic analog of dsRNA, was shown to induce hyporesponsiveness in TLR3-deficient mice and marked responsiveness only in 293 cells expressing TLR3,suggesting a specific recognition to poly(I:C) by TLR3. TLR3 signaling is not elicited by either single-stranded RNA (ssRNA) or dsDNA. TLR3 activation induces cytokine production through a signaling pathway dependent on MyD88. Moreover, poly(I:C) can induce activation of NF-kB and mitogen-activated protein kinases independently of MyD88, and cause dendritic cells to mature.TLR3-?TIR is a TIR-less form of the TLR3 gene generated by deleting the TIR domain (450 bp). This truncated gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR4 Tirless

InvivoGen

Catalog Number: pzero-mtlr4
Description: TLR4 is the receptor for Gram- lipopolysaccharide (LPS). The TLR4 gene was shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). However, TLR4 alone is not sufficient to confer LPS responsiveness. TLR4 requires MD-2, a secreted molecule, to functionaly interact with LPS. Furthermore, a third protein, called CD14, was shown to participates in LPS signaling, leading to NF-?B translocation. This signaling is mediated through the adaptor protein MyD88 but also through a MyD88-independent pathways that involves the (TIR) domain-containing adapter protein (TIRAP). TLR4A-?TIR is a TIR-less form of the TLR4A isoform generated by deleting the TIR domain (498 bp); This truncated gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR5tirless

InvivoGen

Catalog Number: pzero-mtlr5
Description: TLR5 is the Toll-like molecule that recognizes flagellin from both Gram+ and Gram- bacteria. TLR5 was identified by the presence of the TIR domain and is expressed in spleen, PBL and epithelial cells. Activation of the receptor stimulates the production of proinflammatory cytokines, such as TNF-a, through signaling via the adaptor protein MyD88 and the serine kinase IRAK [1, 2]. TLR5 can generate a proinflammatory signal as a homodimer suggesting that it might be the only TLR required for flagellin recognition. Recent data suggest that TLR5 forms heteromeric complexes with TLR4 in macrophages in response to flagellin induction.TLR5-?TIR is a TIR-less form of the TLR5 gene generated by deleting the TIR domain (501 bp). This truncated TLR5 gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR6tirless

InvivoGen

Catalog Number: pzero-mtlr6
Description: TLR6 is expressed in spleen and BPL and, acts as a co-receptor with TLR2 to recognize peptidoglycan and the yeast cell wall particle, zymosan [1,2]. Furthermore, TLR6- and TLR2-deficient mice were reported to be hyporesponsive to mycoplasma macrophage-activating lipopeptide-2 kD (MALP-2), a diacylated lipoprotein, suggesting that TLR2 and TLR6 coordinate the response to this ligand. By contrast, TLR2 is able to recognize bacterial lipoproteins triacylated at the N-terminus cysteine residue. Thus TLR6 appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria.TLR6-?TIR is a TIR-less form of the TLR6 gene generated by deleting the TIR domain (468 bp). This truncated TLR6 gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR7tirless

InvivoGen

Catalog Number: pzero-mtlr7
Description: TLR7 is phylogenetically close to TLR8 and TLR9 and has a higher molecular weight when compared with hTLR1-6, largely as a result of a longer ectodomain. The natural ligand for TLR7 has not been identified yet.However, studies with TLR7-deficient mice have shown that TLR7 recognizes imidazoquinoline compounds, such as R848, a small synthetic antiviral molecule. R848 signaling involves the MyD88-dependent signaling cascade and induces the production of IFN-a, TNF-a and IL-12. Recently, loxoribine and other guanine nucleoside analogs were shown to activate the innate immune system through TLR7 and that this activation requires endosomal maturation.TLR7-?TIR is a TIR-less form of the TLR7 gene generated by deleting the TIR domain (480 bp). This truncated TLR7 gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR8tirless

InvivoGen

Catalog Number: pzero-mtlr8
Description: TLR8 was identified together with TLR7 and TLR9 and is expressed more abundantly in PBL and lung. The natural ligand for TLR8 is still unknown. Recently, human TLR8 and TLR7 were reported to independently confer responsiveness to R848, an imidazoquinoline compound with antiviral activity. Upon R848 stimulation, HEK293 cells transfected with human TLR8 induced NF-kB activation in a dose-dependent manner. In contrast, HEK293 cells expressing murine TLR8 were hyporesponsive to R848.TLR8-?TIR is a TIR-less form of the TLR8 generated by deleting the TIR domain (486 bp). This truncated TLR8 gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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pZERO-mTLR9tirless

InvivoGen

Catalog Number: pzero-mtlr9
Description: TLR9, which is localized intracellularly, is involved in the recognition of specific unmethylated CpG-ODN sequences, that distinguishes bacterial DNA from mammalian DNA. TLR9 engages an intracellular pathway that involves MyD88 leading to NF-?B translocation. TLR9 has been shown to recognize different CpG motifs; the optimal sequences being GTCGTT and GACGTT for hTLR9 and mTLR9 respectively. The ectodomains of hTLR9 and mTLR9 present distinct distribution patterns of leucine-rich repeats. The sequence differences observed in the ectodomains of h- and m-TLR9 may account for the differences in ligand specificity in human versus murine TLR9.TLR9A-?TIR is a TIR-less form of the TLR9 generated by deleting the TIR domain (489 bp). This truncated TLR9 gene is still able to recognize its ligands but is unable to induce the signaling cascade.

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