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 |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
(C3H/HeJ x A/J)F1 | Lung adenoma |
|
Lung |
observed |
|
(C3H/HeJ x A/J)F1 | Lung adenoma |
|
Lung |
observed |
|
A/WySnJ | Lung tumor |
|
Lung |
100 |
|
A/J | Lung tumor |
|
Lung |
100 |
|
SWR/J | Lung tumor |
|
Lung |
100 |
|
O20 | Lung tumor |
|
Lung |
100 |
|
BALB/cJ | Lung tumor |
|
Lung |
100 |
|
129P3/J | Lung tumor |
|
Lung |
89 |
|
BALB/cByJ | Lung tumor |
|
Lung |
83 |
|
PL/J | Lung tumor |
|
Lung |
67 |
|
LP/J | Lung tumor |
|
Lung |
63 |
|
MA/MyJ | Lung tumor |
|
Lung |
100 |
|
SS/Ibg | Lung tumor |
|
Lung |
100 |
|
LS/Ibg | Lung tumor |
|
Lung |
90 |
|
ST/bJ | Lung tumor |
|
Lung |
86 |
|
CBA/J | Lung tumor |
|
Lung |
60 |
|
SM/J | Lung tumor |
|
Lung |
50 |
|
HS/Ibg | Lung tumor |
|
Lung |
35 |
|
C57BL/6J | Lung tumor |
|
Lung |
57 |
|
B10.D2-H1a/(58N)SnJ | Lung tumor |
|
Lung |
40 |
|
B10.A/SgSnJ | Lung tumor |
|
Lung |
40 |
|
C57BL/6ByJ | Lung tumor |
|
Lung |
33 |
|
C57BL/10ScN | Lung tumor |
|
Lung |
30 |
|
SJL/J | Lung tumor |
|
Lung |
29 |
|
DBA/2J | Lung tumor |
|
Lung |
25 |
|
C57BL/10SnJ | Lung tumor |
|
Lung |
22 |
|
C57BL/6N | Lung tumor |
|
Lung |
16 |
|
C57L/J | Lung tumor |
|
Lung |
10 |
|
C3H/HeJ | Lung tumor |
|
Lung |
7 |
|
C3H/2Ibg | Lung tumor |
|
Lung |
5 |
|
AKR/J | Lung tumor |
|
Lung |
0 |
|
C57BR/cdJ | Lung tumor |
|
Lung |
0 |