Mammalian Genome

, Volume 18, Issue 5, pp 300–309

Mammary tumor modifiers in BALB/cJ mice heterozygous for p53

  • Joanna G. Koch
  • Xiangjun Gu
  • Younghun Han
  • Adel K. El-Naggar
  • Melissa V. Olson
  • Daniel Medina
  • D. Joseph Jerry
  • Anneke C. Blackburn
  • Gary Peltz
  • Christopher I. Amos
  • Guillermina Lozano
Article

DOI: 10.1007/s00335-007-9028-2

Cite this article as:
Koch, J.G., Gu, X., Han, Y. et al. Mamm Genome (2007) 18: 300. doi:10.1007/s00335-007-9028-2

Abstract

BALB/c mice are predisposed to developing spontaneous mammary tumors, which are further increased in a p53 heterozygous state. C57BL/6J mice are resistant to induced mammary tumors and develop less than 1% mammary tumors in both wild-type and p53+/− states. To map modifiers of mammary tumorigenesis, we have established F1 and F2 crosses and backcrosses to BALB/cJ (N2-BALB/cJ) and C57BL/6J (N2-C57BL/6J) strains. All cohorts developed mammary carcinomas in p53+/− females, suggesting that multiple loci dominantly and recessively contributed to mammary tumorigenesis. We mapped two modifiers of mammary tumorigenesis in the BALB/cJ strain. Mtsm1 (mammary tumor susceptibility modifier), a dominant-acting modifier, is located on chromosome 7. Mtsm1 is suggestive for linkage to mammary tumorigenesis (p = 0.001). We have analyzed the Mtsm1 region to locate candidate genes by comparing it to a rat modifier region, Mcs3, which shares syntenic conservation with Mtsm1. Expression data and SNPs were also taken into account. Five potential candidate genes within Mtsm1 are Aldh1a3, Chd2, Nipa2, Pcsk6, and Tubgcp5. The second modifier mapped is Mtsm2, a recessive-acting modifier. Mtsm2 is located on chromosome X and is significantly linked to mammary tumorigenesis (p = 1.03 × 10−7).

Supplementary material

335_2007_9028_MOESM1_ESM.xls (27 kb)
Supplementary material

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Joanna G. Koch
    • 1
  • Xiangjun Gu
    • 2
  • Younghun Han
    • 2
  • Adel K. El-Naggar
    • 3
  • Melissa V. Olson
    • 1
  • Daniel Medina
    • 4
  • D. Joseph Jerry
    • 5
    • 6
  • Anneke C. Blackburn
    • 5
    • 9
  • Gary Peltz
    • 7
  • Christopher I. Amos
    • 2
  • Guillermina Lozano
    • 1
    • 8
  1. 1.The University of Texas Graduate School of Biomedical Sciences and the Department of Cancer GeneticsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of EpidemiologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of PathologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  4. 4.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA
  5. 5.Department of Veterinary and Animal Sciences, Molecular and Cellular Biology ProgramUniversity of MassachusettsAmherstUSA
  6. 6.Pioneer Valley Life Sciences InstituteSpringfieldUSA
  7. 7.Roche Palo AltoPalo AltoUSA
  8. 8.Department of Cancer GeneticsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  9. 9.John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia

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