{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:38:11Z","timestamp":1790937491751,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tristetraprolin (TTP) is a mRNA-destabilizing protein that binds to AU-rich elements in labile transcripts, such as the mRNA encoding TNF, and promotes their deadenylation and degradation. TTP-deficient (knockout [KO]) mice exhibit an early-onset, severe inflammatory phenotype, with cachexia, erosive arthritis, left-sided cardiac valvulitis, myeloid hyperplasia, and autoimmunity, which can be prevented by injections of anti-TNF Abs, or interbreeding with TNF receptor-deficient mice. To determine whether the excess TNF that causes the TTP KO phenotype is produced by myeloid cells, we performed myeloid-specific disruption of Zfp36, the gene encoding TTP. We documented the lack of TTP expression in LPS-stimulated bone marrow-derived macrophages from the mice, whereas fibroblasts expressed TTP mRNA and protein normally in response to serum. The mice exhibited a minimal phenotype, characterized by slight slowing of weight gain late in the first year of life, compared with the early-onset, severe weight loss and inflammation seen in the TTP KO mice. Instead, the myeloid-specific TTP KO mice were highly and abnormally susceptible to a low-dose LPS challenge, with rapid development of typical endotoxemia signs and extensive organ damage, and elevations of serum TNF levels to 110-fold greater than control. We conclude that myeloid-specific TTP deficiency does not phenocopy complete TTP deficiency in C57BL\/6 mice under normal laboratory conditions, implying contributions from other cell types to the complete phenotype. However, myeloid cell TTP plays a critical role in protecting mice against LPS-induced septic shock, primarily through its posttranscriptional regulation of TNF mRNA stability.<\/jats:p>","DOI":"10.4049\/jimmunol.1103700","type":"journal-article","created":{"date-parts":[[2012,4,10]],"date-time":"2012-04-10T01:07:12Z","timestamp":1334020032000},"page":"5150-5159","source":"Crossref","is-referenced-by-count":107,"title":["Myeloid-Specific Tristetraprolin Deficiency in Mice Results in Extreme Lipopolysaccharide Sensitivity in an Otherwise Minimal Phenotype"],"prefix":"10.1093","volume":"188","author":[{"given":"Lian-Qun","family":"Qiu","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J","family":"Stumpo","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry J","family":"Blackshear","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health , Research Triangle Park, NC 27709"},{"name":"Department of Medicine, Duke University Medical Center , Durham, NC 27710"},{"name":"Department of Biochemistry, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,5,15]]},"reference":[{"key":"2025032410095819300_r1","first-page":"119","article-title":"Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate","volume":"4","author":"Varnum","year":"1989","journal-title":"Oncogene"},{"key":"2025032410095819300_r2","doi-asserted-by":"crossref","first-page":"19185","DOI":"10.1016\/S0021-9258(17)30642-7","article-title":"A growth factor-inducible nuclear protein with a novel cysteine\/histidine repetitive sequence","volume":"265","author":"DuBois","year":"1990","journal-title":"J. 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