Reference SummaryShoemaker AR, Proc Natl Acad Sci U S A 1998 Sep 1;95(18):10826-31
Title |
A resistant genetic background leading to incomplete penetrance of intestinal neoplasia and reduced loss of heterozygosity in ApcMin/+ mice. |
Authors |
Shoemaker AR; Moser AR; Midgley CA; Clipson L; Newton MA; Dove WF |
Journal |
Proc Natl Acad Sci U S A |
Volume |
95 |
Issue |
18 |
Year |
1998 |
Pages |
10826-31 |
Abstract |
Previous studies of Min/+ (multiple intestinal neoplasia) mice on a sensitive genetic background, C57BL/6 (B6), showed that adenomas have lost heterozygosity for the germ-line ApcMin mutation in the Apc (adenomatous polyposis coli) gene. We now report that on a strongly resistant genetic background, AKR/J (AKR), Min-induced adenoma multiplicity is reduced by about two orders of magnitude compared with that observed on the B6 background. Somatic treatment with a strong mutagen increases tumor number in AKR Min/+ mice in an age-dependent manner, similar to results previously reported for B6 Min/+ mice. Immunohistochemical analyses indicate that Apc expression is suppressed in all intestinal tumors from both untreated and treated AKR Min/+ mice. However, the mechanism of Apc inactivation in AKR Min/+ mice often differs from that observed for B6 Min/+ mice. Although loss of heterozygosity is observed in some tumors, a significant percentage of tumors showed neither loss of heterozygosity nor Apc truncation mutations. These results extend our understanding of the effects of genetic background on Min-induced tumorigenesis in several ways. First, the AKR strain carries modifiers of Min in addition to Mom1. This combination of AKR modifiers can almost completely suppress spontaneous intestinal tumorigenesis associated with the Min mutation. Second, even on such a highly resistant genetic background, tumor formation continues to involve an absence of Apc function. The means by which Apc function is inactivated is affected by genetic background. Possible scenarios are discussed. |
Links |
J:49809 – MGI References 9724789 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| AK.B6-ApcMin/+ | Intestine - Large Intestine tumor |
|
Intestine - Large Intestine |
5.6 |
|
| AK.B6-ApcMin/+ | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
25 - 39 |
||
| AKR/J | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
2.7 |
||
| C57BL/6J | Intestine - Small Intestine tumor |
|
Intestine - Small Intestine |
observed |
|
| AK.B6-ApcMin/+ | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
| AK.B6-ApcMin/+ | Intestine - Small Intestine tumor |
|
Intestine - Small Intestine |
observed |
|
| AK.B6-ApcMin/+ | Intestine adenoma |
|
Intestine |
79 - 100 |
|
| C57BL/6J | Intestine tumor | Intestine |
0 |