Fine mapping and characterization of candidate lung tumor resistance genes for the Par2 locus on mouse chromosome 18.

TitleFine mapping and characterization of candidate lung tumor resistance genes for the Par2 locus on mouse chromosome 18.
Publication TypeJournal Article
Year of Publication2000
AuthorsZhang, Z, Lin, L, Liu, G, Wang, M, Hill, J, Wang, Y, You, M, Devereux, TR
JournalExp Lung Res
Date Published2000 Dec
KeywordsAdenoma, Animals, Animals, Congenic, Chromosome Mapping, Disease Models, Animal, DNA, Neoplasm, Female, Genetic Markers, Genetic Predisposition to Disease, Lung Neoplasms, Male, Mice, Mice, Inbred BALB C, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Pregnancy, Sequence Analysis, DNA

In a number of recent studies, a lung tumor resistance locus designated either Par2 or Pas7 was mapped to distal chromosome 18 in crosses between susceptible A/J and more resistant BALB/c mice. This locus is important in that it accounts for as much as 60% of the difference in lung tumor susceptibility between the A/J and BALB/c mice, both of which contain the susceptible allele of Kras2, a marker and strong candidate for the major lung tumor susceptibility gene on mouse chromosome 6. We have now fine-mapped the Par2 locus by using congenic mice that were constructed by placing part of chromosome 18 from the susceptible A/J onto the genetic background of lung tumor-resistant BALB/c mice. After 7 generations of backcrossing, N7 mice that carried 28 cM of the A/J quantitative trait locus (QTL) region were crossed to the BALB/c to generate the N8 generation. Congenic strains (N8) that contain various QTL regions were generated. N9 mice, generated from N8 males x 3 BALB/c females, were genotyped in the region of the Par2 locus and treated with an initiating dose of urethane and allowed to form lung tumors over 6 months. The mice were killed and the lung tumors counted. With this cross the Par2 locus was narrowed to a 6-cM region. Potential candidate genes in this region include Smad4, Smad2, and Dcc. Previously, we excluded Smad4 and Smad2 as candidates for Par2 based on the lack of functional polymorphism(s) and differential expression in lungs from A/J and BALB/c mice. In this study, no polymorphism of the coding sequence of Dcc was observed between A/J and BALB/c mice. Further fine mapping and positional cloning are required for the identification of the Par2 gene.

Alternate JournalExp Lung Res
PubMed ID11195460
Grant ListCA58554 / CA / NCI NIH HHS / United States
CA78797 / CA / NCI NIH HHS / United States

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