Novel isoforms of murine intercellular adhesion molecule-1 generated by alternative RNA splicing.
Intercellular adhesion molecule-1 (ICAM-1)-deficient mice, produced by homologous recombination and previously recognized to be devoid of the common form of ICAM-1, are shown to express residual amounts of ICAM-1 Ag in thymus and lung. We demonstrate that this expression of ICAM-1 is possible because the mutated exon 5 in these animals has been skipped by alternative splicing of RNA. Three different alternative isoforms of ICAM-1 are expressed in mutant mice. Moreover, two of these isoforms are expressed in wild-type mice together with two additional alternative isoforms that cannot be produced in mutant mice. All alternatively spliced isoforms of ICAM-1 detected are missing complete extracellular Ig domains. In both mutant and wild-type mice, expression of alternatively spliced isoforms is up-regulated following stimulation of animals with LPS. Furthermore, all alternative isoforms of ICAM-1, except one, retain the ability to bind to the well-recognized ICAM-1 counter-receptor LFA-1. These findings, along with the restricted tissue distribution in mutant mice, indicate that alternative isoforms of ICAM-1 are significant physiologic adhesion structures which could play a distinct role in the functioning of the immune system of intact animals.
King
P D
PD
Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
Sandberg
E T
ET
Selvakumar
A
A
Fang
P
P
Beaudet
A L
AL
Dupont
B
B
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins; D017154:Stromal Cells; D013950:Thymus Gland / Q000166:cytology; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1