Abstract: |
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. |
Keywords: |
controlled study; nonhuman; flow cytometry; polymerase chain reaction; animal cell; mouse; animal; mice; animal tissue; gene expression; cell line; animal experiment; mice, mutant strains; immunoglobulin; transfection; mice, inbred c57bl; monoclonal antibody; rna; immunoenzyme techniques; molecular sequence data; hybrid protein; recombinant fusion proteins; tissue distribution; thymus gland; rna, messenger; alternative splicing; alternative rna splicing; base sequence; lipopolysaccharide; up-regulation; stroma cell; stromal cells; cell adhesion; thymocyte; intercellular adhesion molecule 1; mutant; intercellular adhesion molecule-1; lymphocyte function-associated antigen-1; cho cell; ribonuclease; lipopolysaccharides; lymphocyte function associated antigen 1; intraperitoneal drug administration; priority journal; article; support, u.s. gov't, p.h.s.
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