Tlr4 KO Mice

Catalog Number: C001234

Strain Name: C57BL/6NCya-Tlr4em1/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

Toll-like receptor 4 (TLR4), encoded by the human TLR4 gene, is a type I transmembrane protein primarily expressed in monocytes and macrophages. As a crucial component of the innate immune system, TLR4 recognizes pathogen-associated molecular patterns (PAMPs) from microorganisms and damage-associated molecular patterns (DAMPs) from injured tissues. Its main function involves detecting lipopolysaccharides (LPS) from Gram-negative bacteria and initiating intracellular signaling via NF-κB or JNK/SAPK pathways. Additionally, TLR4 recognizes other PAMPs such as lipoteichoic acid (LTA) and double-stranded RNA (dsRNA), playing a pivotal role in the activation of innate immune responses. Research has demonstrated that TLR4 is involved in inflammation, antiviral defense, tumor therapy, and immune regulation. Upon activation, TLR4 triggers downstream signaling pathways, leading to the secretion of cytokines, type I interferons, and other pro-inflammatory mediators critical for innate immune responses.

This strain is a Tlr4 knockout (Tlr4 KO) mouse model utilizing gene editing technology to knock out the Tlr4 gene homologous to the human TLR4 gene in mice. Homozygous Tlr4 KO mice are viable and fertile and exhibit a variety of phenotypes associated with immune responses, including hyporesponsiveness to bacterial lipopolysaccharide (LPS) and elevated levels of respiratory syncytial virus.

Strain Strategy

The Tlr4 gene is located on mouse chromosome 4, and exon 2 of this gene was deleted.



Applications

  • Innate immune response studies;
  • PAMP and DAMP studies;
  • Respiratory syncytial virus research;
  • Inflammatory response, anti-viral infection and tumor therapy studies.


Validation Data

1. Detection of Tlr4 gene expression in various tissues


Figure 1. Detection of Tlr4 gene expression in heart, liver, stomach and spleen tissues of female and male 8-week-old wild-type mice (WT) and Tlr4 KO mice. RT-qPCR detection results showed that there was no Tlr4 mRNA expression in heart, liver, stomach and spleen tissues of Tlr4 KO mice.

ND: Not detected.

 

Publications

[1] Cheng L, Tang X, He Y, Ju B, Wang H. A Δ42PD1 fusion-expressing DNA vaccine elicits enhanced adaptive immune response to HIV-1: the key role of TLR4. Virol J. 2022 Nov 1;19(1):174.
[2] Zhu F, Ma J, Li W, Liu Q, Qin X, Qian Y, Wang C, Zhang Y, Li Y, Jiang D, Wang S, Xia P. The orphan receptor Nur77 binds cytoplasmic LPS to activate the non-canonical NLRP3 inflammasome. Immunity. 2023 Apr 11;56(4):753-767.e8.
[3] Luo JQ, Ren H, Chen MY, Zhao Q, Yang N, Liu Q, Gao YC, Zhou HH, Huang WH, Zhang W. Hydrochlorothiazide-induced glucose metabolism disorder is mediated by the gut microbiota via LPS-TLR4-related macrophage polarization. iScience. 2023 Jun 15;26(7):107130.