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 th e 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 ski pped by alternative splicing of RNA. Three different alternative isofo rms of ICAM-1 are expressed in mutant mice. Moreover, two of these iso forms are expressed in wild-type mice together with two additional alt ernative isoforms that cannot be produced in mutant mice. All alternat ively spliced isoforms of ICAM-1 detected are missing complete extrace llular Ig domains. In both mutant and wild-type mice, expression of al ternatively spliced isoforms is up-regulated following stimulation of animals with LPS. Furthermore, all alternative isoforms of ICAM-1, exc ept one, retain the ability to bind to the well-recognized ICAM-1 coun ter-receptor LFA-1. These findings, along with the restricted tissue d istribution 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 animal s.