Reference SummaryLin L, Exp Lung Res 1998 Jul-Aug;24(4):481-97

Title

Additional evidence that the K-ras protooncogene is a candidate for the major mouse pulmonary adenoma susceptibility (Pas-1) gene.

Authors

Lin L; Festing MF; Devereux TR; Crist KA; Christiansen SC; Wang Y; Yang A; Svenson K; Paigen B; Malkinson AM; You M

Journal

Exp Lung Res

Volume

24

Issue

4

Year

1998

Pages

481-97

Abstract

A locus for mouse pulmonary adenoma susceptibility, Pas-1, has been mapped on distal chromosome 6, where the K-ras gene is located. Allele-specific activation and expression of the K-ras allele from the susceptible parent has been observed in lung tumors from F1 hybrid mice. We report here genetic mapping of lung tumor susceptibility genes in urethane-treated A x B and B x A recombinant inbred (RI) mice using microsatellite markers to seek further evidence for the K-ras gene as candidate for Pas-1. The K-ras genotype differs between the A/J and C57BL/6J progenitors of the RI strains, and distal chromosome 6 contained a major lung tumor susceptibility determinant in the RI mice. Additional evidence that Pas-1 is K-ras involved linkage analysis of (A/JOLaHsd x BALB/ cOLaHsd) F2 intercross mice whose parents shared the same K-ras genotype. In contrast to the results with the A x B and B x A RI strains, no distal chromosome 6 site was significantly associated with tumor development in these F2 mice. In addition to this major locus, linkage analysis of the RI mice revealed additional quantitative trait loci for susceptibility on chromosomes 10, 17, and 19. These loci may serve as modifiers of Pas-1. The relationship between the K-ras genotype and the frequency of K-ras mutations in urethane-induced lung tumors from the RI mice was also explored. All 18 tumor DNAs from RI mice with high susceptibility contained an AT-->TA transversion at the second base of K-ras codon 61. This was also true for DNAs from 27 of 27 (100%) tumors in mice with high intermediate susceptibility. In RI strains with a low intermediate susceptibility, the DNA from 39 of 47 (83%) tumors contained an AT-->TA transversion at codon 61, and only 13 of 21 (62%) tumors had this mutation in the most resistant group. This reflects a positive correlation between the frequency of K-ras mutations in lung tumors of A x B or B x A RI strains and their susceptibility to lung carcinogenesis. Since K-ras appears to be Pas-1, these results suggest that some RI mice that have the resistant K-ras or Pas-1 allele undergo tumor development by a K-ras-independent route.

Links

J:48996 – Mouse Genome Informatics
9659579 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
A/JOlaHsd Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BALB/cOlaHsd Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

(A/JOlaHsd x BALB/cOlaHsd)F2 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB1 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB10 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB11 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB12 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB13 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB14 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB15 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB17 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB18 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB19 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB2 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB20 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB21 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB23 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB24 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB3 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB4 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB5 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB6 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB7 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB8 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

AXB9 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA1 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA11 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA12 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA13 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA14 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA16 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA17 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA18 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA2 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA20 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA22 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA23 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA24 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA25 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA4 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA7 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA8 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed

BXA9 Lung adenoma
  • urethane (ethyl carbamate)
Lung

observed