NF-IL6 Knockout Mice

Nuclear factor for IL-6 expression (NF-IL6) was originally identified as a nuclear factor binding to a 14-bp palindromic sequence (ACATTGCACAATCT) within an interleukin (IL)-1 responsive element in the human IL-6 gene (1). The cloning of the cDNA encoding human NF-IL6 revealed that it shows a high degree of homology with C/EBP in the carboxy-terminal basic and leucine zipper domains, responsible for DNA binding and dimerization, respectively (2). NF-IL6 recognizes the same nucleotide sequences as C/EBP. Both proteins bind to a variety of the divergent nucleotide sequences with different affinity, the consensus sequence is T(T/G)NNGNNAA(T/G). The NF-IL6 gene is intronless, and produces two proteins, liver-enriched transcriptional activator protein (LAP, equivalent to NF-IL6) and liver inhibitory protein (LIP) by alternative usage of two AUG initiation codons within the same open reading frame (3). LIP contains the DNA binding and dimerization domains but is devoid of the N terminal transcriptional activation domain, and therefore behaves as an antagonist of LAP-induced transcription.