Identification of novel modifier loci of Apc Min affecting mammary tumor development.
Genetic background affects the susceptibility to mammary tumor development in Apc(Min/+) mice. Here we report the identification of four novel modifier loci that influence different aspects of mammary tumor development in Apc(Min/+) mice. Analysis of tumor development in a backcross of (FVBB6 Apc(Min/+)) x B6 Apc(Min/+) mice has identified a modifier on chromosome 9 that significantly affects tumor multiplicity, and a modifier on chromosome 4 that significantly affects tumor latency and affects tumor number with suggestive significance. This modifier was also identified in a backcross involving 129X1/SvJ and B6 Apc(Min/+) mice. A modifier on chromosome 18 specifically affects tumor latency but not tumor number. Kaplan-Meier analysis suggests there is at least an additive interaction affecting tumor latency between the loci on chromosomes 4 and 18. We also identified a modifier locus on chromosome 6 that interacts with the loci on chromosome 4 and chromosome 9 to affect tumor number. These results suggest that multiple genetic loci control different aspects of mammary tumor development. None of these modifiers is associated with intestinal tumor susceptibility, which indicates that these modifiers act on tumor development in a tissue-specific manner.
Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA.
Hua
H
Wang
Douglas
D
Teske
Alyssa
A
Tess
Rebecca
R
Kohlhepp
YounJeong
Y
Choi
Christina
C
Kendziorski
Amy Rapaich
AR
Moser
D000477:Alkylating Agents / Q000633:toxicity; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D015987:Effect Modifier, Epidemiologic; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D006965:Hyperplasia / Q000235:genetics; D007414:Intestinal Neoplasms / Q000235:genetics; D008297:Male; D008321:Mammary Glands, Animal / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000453:epidemiology* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL
D000477:Alkylating Agents; D005038:Ethylnitrosourea