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

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