The ROSA26 LacZ-neo(R) insertion confers resistance to mammary tumors in Apc(Min/+) mice

B6.129S7-Girosa26 (ROSA26) mice carry a LacZ-neo(R) insertion on Chromosome (Chr) 6, made by promoter trapping with AB1 129 ES cells. Female C57BL/6J Apc(Min)/+ (B6 Min/+) mice are very susceptible to the induction of mammary tumors after treatment with ethylnitrosourea (ENU). However, ENU-treated B 6 mice carrying both Apc(Min) and ROSA26 are resistant to mammary tumor for mation. Thus, ROSA26 mice carry a modifier of Min-induced mammary tumor sus ceptibility. We have previously mapped the modifier to a 4 -cM interval of 129-derived DNA that also contains the ROSA26 insertion. Here we report add itional evidence for the effect of the ROSA26 insertion on mammary tumor fo rmation. To test the hypothesis that the resistance was due to a linked mod ifier locus, we utilized two approaches. We have derived and tested two lin es of mice that are congenic for 129-derived DNA within the minimal modifie r interval and show that they are as susceptible to mammary tumors as are B 6 mice. Additionally, we analyzed a backcross population segregating for th e insertion and show that mice carrying the insertion are more resistant to mammary tumor development than are mice not carrying the insertion. Thus, the resistance is nor due to a 129-derived modifier allele, but must be due to the ROSA26 insertion. In addition, the effect of the ROSA26 insertion c an be detected in a backcross population segregating for other mammary modi fiers.