Endotoxin triggers some of the strongest responses mammalian immune cells can mount, yet the receptor that relays its signal had never been found. The resistant mice offered a genetic route to it.
Researchers at the University of Texas Southwestern Medical Center mapped the resistance in mice to a single gene, Tlr4. In C3H/HeJ mice, one mutation swapped proline for histidine at position 712 of the protein. A second resistant strain lacked a working gene entirely.
Tlr4 proved to be the receptor that lets mammalian cells detect endotoxin, and Bruce Beutler shared the 2011 Nobel Prize in Physiology or Medicine for the discovery. It also explains why trace endotoxin in a reagent can steer a cell experiment, since the cells carry a sensor built for that molecule.
Read the original study
Poltorak et al., Science, 1998 · doi.org/10.1126/science.282.5396.2085
One amino acid pointed to the endotoxin receptor.
Source
- Poltorak, A., He, X., Smirnova, I., Liu, M. Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., & Beutler, B. (1998). Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science, 282(5396), 2085–8. https://doi.org/10.1126/science.282.5396.2085