Mammary tumor modifiers in BALB/cJ mice heterozygous for p53

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,...

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Bibliographic Details
Published in:	Mammalian genome Vol. 18; no. 5; pp. 300 - 309
Main Authors:	Koch, Joanna G, Gu, Xiangjun, Han, Younghun, El-Naggar, Adel K, Olson, Melissa V, Medina, Daniel, Jerry, D Joseph, Blackburn, Anneke C, Peltz, Gary, Amos, Christopher I, Lozano, Guillermina
Format:	Journal Article
Language:	English
Published:	United States Springer Nature B.V 01-05-2007
Subjects:	Animals Crosses, Genetic Female Genes, p53 Genetic Predisposition to Disease Heterozygote Male Mammary Neoplasms, Animal - genetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Rats Specific Pathogen-Free Organisms
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Summary:	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 x 10(-7)).
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0938-8990 1432-1777
DOI:	10.1007/s00335-007-9028-2