Reference SummaryChen B, Proc Natl Acad Sci U S A 1994 Feb 15;91(4):1589-93

Title

 The second intron of the K-ras gene contains regulatory elements associated with mouse lung tumor susceptibility.

Authors

 Chen B; Johanson L; Wiest JS; Anderson MW; You M

Journal

 Proc Natl Acad Sci U S A

Volume

 91

Issue

 4

Year

 1994

Pages

 1589-93

Abstract

 We have previously demonstrated the preferential activation of the K-ras gene from the susceptible A/J parent in lung tumors from F1 mouse hybrids. In the present study, the mechanism of this observation is further investigated. Higher levels of expression of A/J K-ras allele were detected in lung adenomas (30 of 30) from the C3A mouse. In addition, three K-ras alleles, designated as susceptible (Ks), intermediate (Ki), or resistant (Kr), were identified by sequence analysis of the second intron of the K-ras gene from 32 strains of mice. These K-ras alleles are associated with differences in mouse lung tumor susceptibility. All Kr alleles have a tandem 37-bp direct repeat (nt 282-355) in the second intron of the K-ras gene. Ks and Ki alleles have only one copy of the 37-bp sequence (nt 282-318). Ks strains have three base variations at nt 288, 296, and 494, and Ki strains have two base variations at nt 288 and 494 in the second intron of the K-ras gene. Differential protein-binding patterns were observed in gel-mobility-shift experiments between the duplicated 37-bp sequence of the Kr allele and the single 37-bp sequence of the Ks and Ki alleles. DNase I footprinting assay revealed protein binding sites in the second intron of the K-ras gene that correspond to the tandem repeat sequences. Our data suggest that higher expression of the A/J allele relative to C3H allele may be responsible for the allele-specific activation of the K-ras gene in lung tumors from F1 hybrid mice.

Links

 J:16946 – MGI References
8108449 – National Library of Medicine/PubMed

Strain Notes

Strain Note
129P3/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
A/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
AKR/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
A/WySnJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
B10.A/SgSnJ The reference did not specify the gene carried over in this congenic strain.
The reference groups strains by differences in the 2nd intron of their Kras2 gene.
B10.D2-H1a/(58N)SnJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
These mice were from The Jackson Laboratory.
BALB/cByJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
BALB/cJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C3H/2Ibg The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C3H/HeJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57BL/10ScN The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57BL/10SnJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57BL/6ByJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57BL/6J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57BL/6N The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57BR/cdJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
C57L/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
CBA/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
DBA/2J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
HS/Ibg "inbred strain"
The reference groups strains by differences in the 2nd intron of their Kras2 gene.
LP/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
LS/Ibg The reference groups strains by differences in the 2nd intron of their Kras2 gene.
MA/MyJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
O20 The reference groups strains by differences in the 2nd intron of their Kras2 gene.
PL/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
SJL/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
SM/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.
SS/Ibg The reference groups strains by differences in the 2nd intron of their Kras2 gene.
ST/bJ The reference groups strains by differences in the 2nd intron of their Kras2 gene.
SWR/J The reference groups strains by differences in the 2nd intron of their Kras2 gene.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(C3H/HeJ x A/J)F1 Lung adenoma
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
 Lung

observed
(C3H/HeJ x A/J)F1 Lung adenoma
  • vinyl carbamate (VC)
 Lung

observed
A/WySnJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
A/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
SWR/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
O20 Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
BALB/cJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
129P3/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

89
BALB/cByJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

83
PL/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

67
LP/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

63
MA/MyJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
SS/Ibg Lung tumor
  • urethane (ethyl carbamate)
 Lung

100
LS/Ibg Lung tumor
  • urethane (ethyl carbamate)
 Lung

90
ST/bJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

86
CBA/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

60
SM/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

50
HS/Ibg Lung tumor
  • urethane (ethyl carbamate)
 Lung

35
C57BL/6J Lung tumor
  • urethane (ethyl carbamate)
 Lung

57
B10.D2-H1a/(58N)SnJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

40
B10.A/SgSnJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

40
C57BL/6ByJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

33
C57BL/10ScN Lung tumor
  • urethane (ethyl carbamate)
 Lung

30
SJL/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

29
DBA/2J Lung tumor
  • urethane (ethyl carbamate)
 Lung

25
C57BL/10SnJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

22
C57BL/6N Lung tumor
  • urethane (ethyl carbamate)
 Lung

16
C57L/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

10
C3H/HeJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

7
C3H/2Ibg Lung tumor
  • urethane (ethyl carbamate)
 Lung

5
AKR/J Lung tumor
  • urethane (ethyl carbamate)
 Lung

0
C57BR/cdJ Lung tumor
  • urethane (ethyl carbamate)
 Lung

0