Genetic Studies on Eµ-myc Transgenic Mice

Transgenic mice carrying the c-myc oncogene under the control of the Ig heavy chain enhancer (“Eµ-myc” mice)(Cory and Adams, 1988; Harris et al., 1988a) develop B lineage tumors within the first year of life, and offer a reproducible and attractive system with which to dissect the genetic and cellular processes involved in tumorigenesis. Because the founder mouse of this strain was a (B6xSJL) F2 animal, the primary transgenic mouse stock has been maintained by continual crossing of transgenic animals to (B6xSJL) F1 hybrids. The line so maintained (genetically equivalent to an F2, and thus termed FE2) continously segregates the B6 and SJL genomes. Although over time the amount of each component averages 50%, any locus in any individual mouse could have 2 B6 alleles, 2 SJL alleles, or one of each. Thus, it is not surprising that considerable heterogeneity has been observed in the rate with which individual (B6xSJL)FE2-Eµ-myc transgenic mice develop visible tumors and die (Harris et al 1988b). In fact, three phases of tumor onset and death have been described in this stock; a lag phase, a rapid onset phase for some animals, and a slower onset phase for the remaining mice (Harris et al, 1988b). With the aim of reducing this genotypic and phenotypic variability, Eµ-myc mice have been repeatedly backcrossed to the parental B6 and SJL backgrounds.