Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  4
• Reference
  J:128481 Wang H, et al., Identification of novel modifier loci of Apc Min affecting mammary tumor development. Cancer Res. 2007 Dec 1;67(23):11226-33
• ID
  MGI:3802639

Genes

Gene	Assay Type
Mmom2	resistance/susceptibility
D4Mit82	PCR amplified length variant
D4Mit26	PCR amplified length variant

Notes

• Experiment
  Genetic modifiers of ENU-induced mammary tumor susceptibility on an Apc^min genetic background were mapped using mouse backcross populations. Linkage analysis was performed on 307 female (FVB/NTac x C57BL/6J-Apc^Min)F1 x C57BL/6J-Apc^Min backcross animalstreated with ENU between 35 to 45 days of age. Animals were sacrificed 75 days after mutagenesis treatment and genotyped at 102 microsatellite markers (average spacing = 20 cM). (FVB/NTac x C57BL/6J-Apc^Min)F1 hybrids are resistant to ENU-induced mammarytumors compared to C57BL/6J-Apc^Min suggesting protective genes are contributed by the FVB/NTac strain. A separate population of 80 female (129X1/SvJ x C57BL/6J-Apc^Min)F1 x C57BL/6J-Apc^Min backcross animals treated with the same ENU mutagenesis scheme were analyzed for 79 polymorphic loci. QTLs identified in this study are tissue-specific for mammary tumors and do not appear to have an effect on intestinal tumor development.
  
  On mouse Chromosome 9, significant linkage to mammary tumor number mapped to 55 cM near D9Mit182 (LOD=3.1). This locus is named Mmom1 (mammary modifier of Min 1). FVB/NTac-derived alleles at Mmom1 confer a 30% decrease in mammary tumor number compared to females homozygous for C57BL/6J-derived alleles. Apmt2 at 55 cM is a previously identified mammary tumor susceptibility QTL coinciding with Mmom1. This locus is orthologous to human Chromosome 3p21-p23, a region associated with loss of heterozygosity and hypermethylation in human lung and breast cancers.
  
  Suggestive linkage tomammary tumor number mapped to 32.5 cM mouse Chromosome 4 near D4Mit82 (LOD=2.1) and is named Mmom2 (mammary modifier of Min 2). FVB/NTac-derived alleles at Mmom2 confer a 24% decrease in mammary tumor number compared to females homozygous for C57BL/6J-derived alleles. This locus also displays significant linkage to tumor latency (LOD=3.5) with FVB/NTac-derived alleles conferring increased tumor latency time. Mmom2 was independently identified in the (129X1/SvJ x C57BL/6J-Apc^Min)F1 x C57BL/6J-Apc^Min backcross with linkageto mammary tumor number (LOD=2.4) and tumor latency (LOD=3) at D4Mit26 (42.5 cM). Heterozygosity for 129X1/SvJ-derived alleles at Mmom2 confers decreased tumor number and increased tumor latency compared to homozygosity for C57BL/6J-derived alleles. The Mmom2 locus is orthologous to a region of human Chromosome 9q known for loss of heterozygosity in human breast cancers.
  
  Mmom3 (mammary modifier of Min 3) is located at 38.5 cM on mouse Chromosome 6 near D6Mit31 (LOD=1.1). Althoughthislocus does not reach statistical significance on its own, it displays additive interactive effects with Mmom1 and Mmom2. Animals heterozygous for FVB/NTac-derived alleles at both Mmom1 and Mmom3 displayed a 50% decrease in mammary tumor number compared to animals homozygous at both loci (joint LOD=4.46). A similar effect is seen between Mmom2 and Mmom3 with FVB/NTac-derived alleles conferring decreased mammary tumor number.
  
  Linkage to tumor latency mapped to 25 cM on mouse Chromosome 18 near D18Mit24 (LOD=2.6).This locus is named Mmom4 (mammary modifier of Min 4) and is located 10 cM distal to Apc. An additive effect was detected between Mmom2 and Mmom4. Female animals heterozygous for FVB/NTac-derived alleles at both loci displayed significantly increased tumor latency (P<0.001).