AHR NULL ALLELES - DISTINCTIVE OR DIFFERENT

Two independent laboratories have generated Ahr ''null'' or ''knockout '' mice that share some common characteristics but also have distinct phenotypes. In this Commentary, we will discuss our view of the candid ate variables,that might account for these differences. More important ly, we hope that this discussion can identify important parameters to be assessed by investigators in the process of characterizing their ow n modified loci. The variables that we have considered include the pos sibility that different targeting strategies can result in altered pro ducts with unsuspected function or that the targeting event itself can alter the function of neighboring genes. Further, genetic background can have an important influence on phenotype, and differences in genom e can be introduced during derivation by the type of embryonic stem ce lls used and by the random segregation of parental genes in the F2 gen eration of line propagation. In addition, phenotype may be acutely sen sitive to environmental variables, such as pathogen and chemical expos ure and stress introduced by crowding and disease. Finally, we discuss approaches to resolving differences between null mice and propose a p artial solution, the institution of a repository for detailed informat ion on targeted alleles that may not typically be allowed in today's ' 'fast paced'' scientific publications. BIOCHEM PHARMACOL 56;7:781-787, 1998. (C) 1998 Elsevier Science Inc.