Just how does the cII selection system work in Muta Mouse?

The lambda CII protein is an essential component in the lytic vs. lysogeny decision a bacteriophage makes upon infection of a host at low temperatures. The protein interacts with numerous phage promoters modulating the expression of the CI repressor, thus providing the mechanism for lysogenization soon after infection. The Big Blue and Muta Mouse are two widely used in vivo mutational model systems. The assays rely on retrievable lambda-based transgenes housing mutational targets (lacI or lacZ, respectively). The transgenes provide an elegant vehicle for the quantification of mutations sustained in virtually any tissue of the rodent. The use of the bacteriophage cII locus as an alternative, or additional mutational target for use with the Big Blue rodent system was first reported by Jakubczak et al. ([1996]: Proc Natl Acad Sci USA 93:9073-9078). More recently, this selection assay has been applied successfully to the Muta Mouse (Swiger et al. [1999]: Environ Mol Mutagen 33:201-207). The use of an Hfl bacterial strain and low temperature allows the determination of mutations sustained at the cII locus in either system, with high fidelity. The cII selection assay in the Big Blue relies on the presence of the lambda repressor protein CI. In contrast, the recombinant construct used to make the Muta Mouse transgene lacks functional CI protein. Nevertheless, we report an excellent system for quantifying mutations at the cII locus in Muta Mouse. Just how does cII selection work in the Muta Mouse? Written in the context of lambda recombinant genetics, this paper explores the question further.