Lpsd/Ran of endotoxin-resistant C3H/HeJ mice is defective in mediating lipopolysaccharide endotoxin responses

• DOI: 10.1073/pnas.96.20.11543
• Publication Date: 2002-07-26T14:31:39Z
• Authors: Peter M. C. Wong; Anthony Kang; Hong Chen; Quan Yuan; Peidong Fan; Barnet M. Sultzer; Yuet Wai Kan; Siu-Wah Chung
• Keywords: Ran

C3H/HeJ inbred mice are defective in that they highly resistant to endotoxic shock as compared with normal responder mice. Their B cells and macrophages do not respond significantly when exposed lipopolysaccharide (LPS), whereas from the do. Using a functional assay, we previously isolated cDNA, which encodes for Ran/TC4 GTPase. We now show this gene is mutated mice, accounts their resistance endotoxin stimulation. Sequence analysis of independent mutant Lps(d)/Ran cDNAs splenic reveals consistent single base substitution at position 870, where thymidine replaced cytidine. In situ hybridization maps cDNA mouse chromosome 4. By retroviral transfer, wild-type Lps(n)/Ran but can restore LPS responsiveness cells. Adenoviral transfer vivo rescues endotoxin-sensitive septic shock. Thus Lps/Ran an important target LPS-mediated signal transduction, may be useful therapeutic sequence therapy endotoxemia