THE HUMAN-LEUKOCYTE INTEGRIN CD11A PROMOTER DIRECTS EXPRESSION IN LEUKOCYTES OF TRANSGENIC MICE

The human CD11a molecule is expressed specifically on lymphocytes, mon ocyte/macrophages, and neutrophils, in which it mediates important adh esion-related functions. We used 1.7 kb of regulatory sequences upstre am from the human CD11a gene transcription start site to drive express ion of a modified human CD4 reporter gene in transgenic mice. The tran sgene was expressed in a tissue-specific fashion on all leukocytes and paralleled endogenous mouse CD11a expression. All five founder mice e xpressed the transgene, providing evidence for integration site-indepe ndent expression, However, expression was not proportional to transgen e copy number. These studies indicate that (1) the mutated human CD4 s erves as an excellent reporter for analysis of leukocyte-specific prom oters; (2) the CD11a regulatory unit used here represents a novel reag ent for targeting gene expression to leukocytes; and (3) additional re gulatory regions will be required for copy-number-dependent activity o f CD11a regulatory sequences.