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Publication : Gene targeting yields a CD18-mutant mouse for study of inflammation.

First Author  Wilson RW Year  1993
Journal  J Immunol Volume  151
Issue  3 Pages  1571-8
PubMed ID  8101543 Mgi Jnum  J:13599
Mgi Id  MGI:61784 Doi  10.4049/jimmunol.151.3.1571
Citation  Wilson RW, et al. (1993) Gene targeting yields a CD18-mutant mouse for study of inflammation. J Immunol 151(3):1571-8
abstractText  CD18 is the common beta subunit for the heterodimeric leukocyte integrins that mediate many inflammatory cell adhesion responses including binding to intercellular adhesion molecules 1 and 2. CD18 deficiency in humans causes a severe granulocyte disorder with susceptibility to bacterial infections and high morbidity and mortality. Gene targeting was used to prepare an insertion mutation in the murine CD18 gene. The insertion mutation resulted in a hypomorphic rather than a null allele due to low expression from a cryptic promoter in the plasmid construct. Homozygous mutant mice are viable and fertile, demonstrate a mild granulocytosis, and have 2 or 16% of normal CD18 expression on granulocytes in the resting or activated state, respectively. Mutant mice show an impaired inflammatory response to a chemical peritonitis and delayed rejection of cardiac transplants. These CD18-mutant mice provide a model of the moderate form of the human disease and should be extremely valuable for in vivo analysis of the role of leukocyte integrin-dependent adhesion in inflammatory disease models.
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