First Author | Hardy MP | Year | 2002 |
Journal | Biochem J | Volume | 365 |
Issue | Pt 2 | Pages | 355-67 |
PubMed ID | 11939908 | Mgi Jnum | J:78015 |
Mgi Id | MGI:2183112 | Doi | 10.1042/BJ20020105 |
Citation | Hardy MP, et al. (2002) Multiple regions within the promoter of the murine Ifnar-2 gene confer basal and inducible expression. Biochem J 365(Pt 2):355-67 |
abstractText | The (murine) type I interferon (IFN) receptor, muIfnar-2, is expressed ubiquitously, and exists as both transmembrane and soluble forms. In the present study we show that the gene encoding muIfnar-2 spans approx. 33 kb on mouse chromosome 16, and consists of nine exons and eight introns. The three mRNA splice variants resulting in one transmembrane (muIfnar-2c) and two soluble (muIfnar-2a/2a') mRNA isoforms are generated by alternative RNA processing of the muIfnar-2 gene. Treatment of a range of murine cell lines with a combination of type I and II IFN showed that the muIfnar-2a and -2c mRNA isoforms were up-regulated independently of each other in L929 fibroblasts and hepa-1c1c7 hepatoma cells, but not in M1 myeloid leukaemia cells. Analysis of the 5' flanking region of muIfnar-2 using promoter-luciferase reporter constructs defined three regulatory regions: a region proximal to exon 1, conferring high basal expression, a distal region conferring inducible expression, and a negative regulatory region between the two. These data represent the first promoter analysis of a type I IFN receptor and, taken together with our previous data demonstrating high expression levels and dual biological functions for muIfnar-2a protein, suggests that the regulation of muIfnar-2 isoform expression may be an important way of modulating type I IFN responses. |