Bruce Beutler


Affiliation: University of Texas Southwestern Medical Center
Country: USA


  1. Wang Y, Su L, Morin M, Jones B, Whitby L, Surakattula M, et al. TLR4/MD-2 activation by a synthetic agonist with no similarity to LPS. Proc Natl Acad Sci U S A. 2016;113:E884-93 pubmed publisher
    ..However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS. ..
  2. McAlpine W, Sun L, Wang K, Liu A, Jain R, San Miguel M, et al. Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function. Proc Natl Acad Sci U S A. 2018;115:E11523-E11531 pubmed publisher
    ..Deficiency of WDR41 phenocopied loss of SMCR8. Our findings provide evidence that excessive endosomal TLR signaling resulting from prolonged ligand-receptor contact causes inflammatory disease in SMCR8-deficient mice. ..
  3. Pedersen G, Àdori M, Khoenkhoen S, Dosenovic P, Beutler B, Karlsson Hedestam G. B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS. Proc Natl Acad Sci U S A. 2014;111:E4119-26 pubmed publisher
    ..This study identifies a phenotypically distinct splenic population of TrB-1a cells and establishes that the development of B-1a cells is blocked before this stage in the absence of IκBNS. ..
  4. Siggs O, Popkin D, Krebs P, Li X, Tang M, Zhan X, et al. Mutation of the ER retention receptor KDELR1 leads to cell-intrinsic lymphopenia and a failure to control chronic viral infection. Proc Natl Acad Sci U S A. 2015;112:E5706-14 pubmed publisher
    ..Antiviral immunity was also compromised, with Kdelr1 mutant mice unable to clear an otherwise self-limiting viral infection. These data reveal a nonredundant cellular function for KDELR1, upon which lymphocytes distinctly depend. ..
  5. Turer E, San Miguel M, Wang K, McAlpine W, Ou F, Li X, et al. A viable hypomorphic Arnt2 mutation causes hyperphagic obesity, diabetes and hepatic steatosis. Dis Model Mech. 2018;11: pubmed publisher
    ..These findings establish a requirement for ARNT2-dependent genes in the maintenance of the homeostatic feeding response, necessary for prevention of obesity and obesity-related diseases. ..
  6. McAlpine W, Wang K, Choi J, San Miguel M, McAlpine S, Russell J, et al. The class I myosin MYO1D binds to lipid and protects against colitis. Dis Model Mech. 2018;11: pubmed publisher
    ..Moreover, MYO1D appears to couple cytoskeletal elements to lipid in an ATP-dependent manner. These findings demonstrate that MYO1D is needed to maintain epithelial integrity and protect against DSS-induced colitis. ..
  7. Wang Y, Su L, Morin M, Jones B, Mifune Y, Shi H, et al. Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice. Proc Natl Acad Sci U S A. 2018;115:E8698-E8706 pubmed publisher
    ..Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti-PD-L1 treatment. ..
  8. Wang Y, Cao L, Lee C, Matsuo T, Wu K, Asher G, et al. Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors. Nat Commun. 2018;9:2041 pubmed publisher
    ..The work establishes the first forward genetics screen to uncover the molecular mechanism of innate fear, a basic emotion and evolutionarily conserved survival mechanism. ..
  9. Wang T, Bu C, Hildebrand S, Jia G, Siggs O, Lyon S, et al. Probability of phenotypically detectable protein damage by ENU-induced mutations in the Mutagenetix database. Nat Commun. 2018;9:441 pubmed publisher
    ..We estimate the proportion of essential autosomal genes in Mus musculus (C57BL/6J) and show that viable mutations in essential genes are more likely to induce phenotype than mutations in non-essential genes. ..

More Information


  1. Turer E, McAlpine W, Wang K, Lu T, Li X, Tang M, et al. Creatine maintains intestinal homeostasis and protects against colitis. Proc Natl Acad Sci U S A. 2017;114:E1273-E1281 pubmed publisher
    ..These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury. ..
  2. Wang T, Zhan X, Bu C, Lyon S, Pratt D, Hildebrand S, et al. Real-time resolution of point mutations that cause phenovariance in mice. Proc Natl Acad Sci U S A. 2015;112:E440-9 pubmed publisher
    ..The method described here permits forward genetic analysis in mice, limited only by the rates of mutant production and screening. ..
  3. Zhang Z, Turer E, Li X, Zhan X, Choi M, Tang M, et al. Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice. Proc Natl Acad Sci U S A. 2016;113:E6418-E6426 pubmed
    ..Kbtbd2 was down-regulated in diet-induced obese insulin-resistant mice in a leptin-dependent manner. KBTBD2 is an essential regulator of the insulin-signaling pathway, modulating insulin sensitivity by limiting p85α abundance. ..
  4. Beutler B. Innate immunity and the new forward genetics. Best Pract Res Clin Haematol. 2016;29:379-387 pubmed publisher
    ..We have created more than 100,000 coding/splicing mutations. And by screening for defects of innate and adaptive immunity we have discovered many "new" proteins needed for innate immune function. ..
  5. Choi J, Wang K, Zhang D, Zhan X, Wang T, Bu C, et al. IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice. Proc Natl Acad Sci U S A. 2017;114:E1196-E1204 pubmed publisher
    ..These results identify a pathway, present in WT mice and hyperactivated in 53BP1-deficient mice, by which microbiota signal via Toll-like receptors to elicit IgD CSR. ..
  6. Zhang D, Tomisato W, Su L, Sun L, Choi J, Zhang Z, et al. Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5. Proc Natl Acad Sci U S A. 2017;114:E5197-E5206 pubmed publisher
    ..GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body. ..
  7. Tabeta K, Du X, Arimatsu K, Yokoji M, Takahashi N, Amizuka N, et al. An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue. Sci Rep. 2017;7:11717 pubmed publisher
    ..Seal mice represent a model of human osteogenesis imperfecta, and reveal a previously unknown mechanism for splicing "rescue." ..
  8. Sun L, Jiang Z, Acosta Rodriguez V, Berger M, Du X, Choi J, et al. HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections. J Exp Med. 2017;214:3263-3277 pubmed publisher
    ..HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases. ..
  9. Chen Z, Holland W, Shelton J, Ali A, Zhan X, Won S, et al. Mutation of mouse Samd4 causes leanness, myopathy, uncoupled mitochondrial respiration, and dysregulated mTORC1 signaling. Proc Natl Acad Sci U S A. 2014;111:7367-72 pubmed publisher
    ..Samd4 may interface with mTORC1 signaling through an interaction with 14-3-3 proteins and with Akt, which phosphorylates Samd4 in vitro. ..