title: The ROSA26 LacZ-neo(R) insertion confers resistance to mammary tumors in Apc(Min/+) mice.
abstract: B6.129S7-Gtrosa26 (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 B6 mice carrying both Apc(Min) and ROSA26 are resistant to mammary tumor formation. Thus, ROSA26 mice carry a modifier of Min-induced mammary tumor susceptibility. We have previously mapped the modifier to a 4-cM interval of 129-derived DNA that also contains the ROSA26 insertion. Here we report additional evidence for the effect of the ROSA26 insertion on mammary tumor formation. To test the hypothesis that the resistance was due to a linked modifier locus, we utilized two approaches. We have derived and tested two lines of mice that are congenic for 129-derived DNA within the minimal modifier interval and show that they are as susceptible to mammary tumors as are B6 mice. Additionally, we analyzed a backcross population segregating for the 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 not due to a 129-derived modifier allele, but must be due to the ROSA26 insertion. In addition, the effect of the ROSA26 insertion can be detected in a backcross population segregating for other mammary modifiers.
authors.affiliation: The Department of Human Oncology, K4/330 CSC 3864, 600 Highland Ave, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Kohlhepp
authors.forename: L F
authors.initials: LF
authors.lastname: Hegge
authors.forename: A R
authors.initials: AR
authors.lastname: Moser
mesh_terms: D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D003433:Crosses, Genetic; D005038:Ethylnitrosourea / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D005819:Genetic Markers / Q000235:genetics; D015994:Incidence; D007763:Lac Operon / Q000235:genetics*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D022661:RNA, Untranslated
chemical_list: D005819:Genetic Markers; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; D005038:Ethylnitrosourea