Reference SummaryHernandez-Porras I, J Pathol 2016 Jun;239(2):206-17
Title |
K-Ras(V14I) -induced Noonan syndrome predisposes to tumour development in mice. | ||||
Authors |
Hernandez-Porras I; Schuhmacher AJ; Garcia-Medina R; Jimenez B; Canamero M; de Martino A; Guerra C | ||||
Journal |
J Pathol | ||||
Volume |
239 | ||||
Issue |
2 | ||||
Year |
2016 | ||||
Pages |
206-17 | ||||
Abstract |
The Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant proportion of NS patients may also develop myeloproliferative disorders (MPDs), including juvenile myelomonocytic leukaemia (JMML). Surprisingly, scarce information is available in relation to other tumour types in these patients. We have previously developed and characterized a knock-in mouse model that carries one of the most frequent KRAS-NS-related mutations, the K-Ras(V14I) substitution, which recapitulates most of the alterations described in NS patients, including MPDs. The K-Ras(V14I) mutation is a mild activating K-Ras protein; thus, we have used this model to study tumour susceptibility in comparison with mice expressing the classical K-Ras(G12V) oncogene. Interestingly, our studies have shown that these mice display a generalized tumour predisposition and not just MPDs. In fact, we have observed that the K-Ras(V14I) mutation is capable of cooperating with the p16Ink4a/p19Arf and Trp53 tumour suppressors, as well as with other risk factors such as pancreatitis, thereby leading to a higher cancer incidence. In conclusion, our results illustrate that the K-Ras(V14I) activating protein is able to induce cancer, although at a much lower level than the classical K-Ras(G12V) oncogene, and that it can be significantly modulated by both genetic and non-genetic events. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. | ||||
Links |
J:241552 – MGI References 27174785 – National Library of Medicine/PubMed |
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Strain Notes
|
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| |||||
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| C57BL/6JOlaHsd | Blood tumor | Blood |
20 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Blood vessel hemangioma | Blood vessel |
0 - 11 |
||
| B6.129-Krastm4.1Bbd/+ | Blood vessel hemangiosarcoma | Blood vessel |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Blood vessel hemangiosarcoma | Blood vessel |
0 - 25 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Blood vessel hemangiosarcoma | Blood vessel |
0 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | CNS - Brain tumor | CNS - Brain |
0 - 11 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Connective tissue - Fibroblast fibrosarcoma | Connective tissue - Fibroblast |
0 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd/+ | Connective tissue - Fibroblast fibrosarcoma | Connective tissue - Fibroblast |
0 - 67 |
||
| B6;129-Krastm4.1Bbd/+ | Epididymis adenoma | Epididymis |
9.1 |
||
| B6;129-Krastm4.1Bbd | Epididymis adenoma | Epididymis |
0 |
||
| B6.129-Krastm4.1Bbd/+ | Intestine - Small Intestine - Duodenum adenocarcinoma | Intestine - Small Intestine - Duodenum |
0 - 17 |
||
| B6;129-Krastm4.1Bbd/+ | Intestine - Small Intestine - Duodenum adenoma | Intestine - Small Intestine - Duodenum |
6.7 - 9.1 |
||
| B6.129-Krastm4.1Bbd/+ | Intestine - Small Intestine - Duodenum adenoma | Intestine - Small Intestine - Duodenum |
0 - 100 |
||
| B6;129-Krastm4.1Bbd/+ | Intestine - Small Intestine - Duodenum adenoma - tubular | Intestine - Small Intestine - Duodenum |
0 - 9.1 |
||
| B6.129-Krastm4.1Bbd/+ | Intestine adenocarcinoma | Intestine |
0 - 17 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Intestine adenocarcinoma | Intestine |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Intestine adenocarcinoma | Intestine |
0 |
||
| B6;129-Krastm4.1Bbd/+ | Intestine adenoma | Intestine |
9.1 - 13 |
||
| B6;129-Krastm4.1Bbd | Intestine adenoma | Intestine |
0 |
||
| B6;129-Krastm4.1Bbd/+ | Leukocyte - Lymphocyte - B-lymphocyte lymphoma | Leukocyte - Lymphocyte - B-lymphocyte |
9.1 - 13 |
||
| B6;129-Krastm4.1Bbd | Leukocyte - Lymphocyte - B-lymphocyte lymphoma | Leukocyte - Lymphocyte - B-lymphocyte |
0 |
||
| [not specified]-Krastm4.1Bbd/+ | Leukocyte - Lymphocyte - B-lymphocyte lymphoma | Leukocyte - Lymphocyte - B-lymphocyte |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Lymphocyte - B-lymphocyte lymphoma | Leukocyte - Lymphocyte - B-lymphocyte |
0 - 33 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd/+ | Leukocyte - Lymphocyte - B-lymphocyte lymphoma | Leukocyte - Lymphocyte - B-lymphocyte |
0 - 33 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte - Lymphocyte - B-lymphocyte lymphoma | Leukocyte - Lymphocyte - B-lymphocyte |
11 - 100 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte - Lymphocyte - T-lymphocyte lymphoma | Leukocyte - Lymphocyte - T-lymphocyte |
0 - 11 |
||
| B6;129-Krastm4.1Bbd/+ | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
9.1 - 27 |
||
| B6;129-Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
20 - 29 |
||
| B6;129 | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
0 - 33 |
||
| B6.129-Krastm4.1Bbd/+ | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
0 - 50 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
0 - 20 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
80 - 100 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Uterus - Uterine horn |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Spleen |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Pancreas |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Intestine - Small Intestine - Duodenum |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Liver |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Urinary bladder |
observed |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd/+ | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
67 - 86 |
||
| B6;129-Krastm4.1Bbd/+ | Leukocyte - Myelocyte (Granulocyte) hyperplasia | Leukocyte - Myelocyte (Granulocyte) |
0 - 18 |
||
| B6;129-Krastm4.1Bbd | Leukocyte - Myelocyte (Granulocyte) hyperplasia | Leukocyte - Myelocyte (Granulocyte) |
29 - 40 |
||
| B6;129-Krastm4.1Bbd/+ | Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic | Leukocyte - Myelocyte (Granulocyte) |
0 - 13 |
||
| B6;129-Krastm4.1Bbd | Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic | Leukocyte - Myelocyte (Granulocyte) |
0 |
||
| B6;129-Krastm4.1Bbd/+ | Leukocyte lymphoma | Leukocyte |
55 - 67 |
||
| B6;129-Krastm4.1Bbd | Leukocyte lymphoma | Leukocyte |
60 - 71 |
||
| B6;129 | Leukocyte lymphoma | Leukocyte |
0 - 50 |
||
| B6.129-Krastm4.1Bbd/+ | Leukocyte lymphoma | Leukocyte |
67 - 100 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Leukocyte lymphoma | Leukocyte |
0 - 25 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Leukocyte lymphoma | Leukocyte |
0 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Leukocyte lymphoma | Leukocyte |
20 - 67 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd/+ | Leukocyte lymphoma | Leukocyte |
29 - 33 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte lymphoma | Leukocyte |
89 - 100 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte lymphoma | Spleen |
observed |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte lymphoma | Kidney |
observed |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte lymphoma | Lung |
observed |
||
| B6;129-Krastm4.1Bbd/+ | Leukocyte lymphoma - lymphoblastic | Leukocyte |
0 - 6.7 |
||
| B6;129-Krastm4.1Bbd | Leukocyte lymphoma - lymphoblastic | Leukocyte |
0 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte lymphoma - lymphoblastic | Leukocyte |
0 - 22 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Leukocyte lymphoma - lymphoblastic | Thymus |
0 - 11 |
||
| B6;129-Krastm4.1Bbd/+ | Liver adenocarcinoma | Liver |
0 - 18 |
||
| B6;129-Krastm4.1Bbd | Liver adenocarcinoma | Liver |
0 |
||
| B6;129-Krastm4.1Bbd/+ | Liver adenoma | Liver |
0 - 9.1 |
||
| B6;129-Krastm4.1Bbd | Liver adenoma | Liver |
0 |
||
| B6;129-Krastm4.1Bbd/+ | Lung adenocarcinoma | Lung |
0 - 18 |
||
| B6;129-Krastm4.1Bbd | Lung adenocarcinoma | Lung |
0 |
||
| B6.129-Krastm4.1Bbd/+ | Lung adenocarcinoma | Lung |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Lung adenocarcinoma | Lung |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Lung adenocarcinoma | Lung |
0 |
||
| [not specified]-Krastm1Bbd/+ Polr2atm1(cre/ERT2)Bbd/+ | Lung adenocarcinoma |
|
Lung |
observed |
|
| B6;129-Krastm4.1Bbd/+ | Lung adenoma | Lung |
0 - 9.1 |
||
| B6;129-Krastm4.1Bbd | Lung adenoma | Lung |
0 |
||
| B6.129-Krastm4.1Bbd/+ | Lung adenoma | Lung |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Lung adenoma | Lung |
0 - 25 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Lung adenoma | Lung |
0 - 100 |
||
| [not specified]-Krastm1Bbd/+ Polr2atm1(cre/ERT2)Bbd/+ | Lung adenoma |
|
Lung |
observed |
|
| [not specified]-Krastm4.1Bbd/+ | Lung adenoma | Lung |
observed |
||
| [not specified]-Krastm4Bbd/+ | Lung tumor |
|
Lung |
0 |
|
| [not specified]-Krastm1Bbd/+ | Lung tumor |
|
Lung |
100 |
|
| [not specified]-Krastm4Bbd/+ Polr2atm1(cre/ERT2)Bbd/+ | Lung tumor |
|
Lung |
0 |
|
| [not specified]-Krastm1Bbd/+ Polr2atm1(cre/ERT2)Bbd/+ | Lung tumor |
|
Lung |
100 |
|
| [not specified]-Polr2atm1(cre/ERT2)Bbd/+ | Lung tumor |
|
Lung |
0 |
|
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | Lymphatic vessel lymphangioma | Thymus |
0 - 20 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd/+ | Mesodermal cell/mesoblast sarcoma - unclassified | Mesodermal cell/mesoblast |
0 - 14 |
||
| B6.129-Krastm4.1Bbd/+ | Pancreas adenocarcinoma | Pancreas |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | Pancreas adenocarcinoma | Pancreas |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | Pancreas adenocarcinoma - ductal | Pancreas |
0 - 20 |
||
| [not specified] | Pancreas adenocarcinoma - ductal |
|
Pancreas |
0 |
|
| [not specified]-Krastm4.1Bbd/+ | Pancreas adenocarcinoma - ductal |
|
Pancreas |
0 |
|
| [not specified]-Krastm4.1Bbd | Pancreas adenocarcinoma - ductal |
|
Pancreas |
0 |
|
| [not specified]-Krastm4Bbd/+ Tg(Cela1-tTA)#Eps Tg(tetO-cre)3Jig | Pancreas adenocarcinoma - ductal |
|
Pancreas |
0 |
|
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | Pancreas pancreatic intraepithelial neoplasia (PanIN) | Pancreas |
0 - 11 |
||
| [not specified] | Pancreas pancreatic intraepithelial neoplasia (PanIN) - high grade |
|
Pancreas |
0 |
|
| [not specified]-Krastm4.1Bbd/+ | Pancreas pancreatic intraepithelial neoplasia (PanIN) - high grade |
|
Pancreas |
14.3 - 37.5 |
|
| [not specified]-Krastm4.1Bbd | Pancreas pancreatic intraepithelial neoplasia (PanIN) - high grade |
|
Pancreas |
60 - 87.5 |
|
| [not specified]-Krastm4Bbd/+ Tg(Cela1-tTA)#Eps Tg(tetO-cre)3Jig | Pancreas pancreatic intraepithelial neoplasia (PanIN) - high grade |
|
Pancreas |
10 - 11 |
|
| [not specified] | Pancreas pancreatic intraepithelial neoplasia (PanIN) - low grade |
|
Pancreas |
0 |
|
| [not specified]-Krastm4.1Bbd/+ | Pancreas pancreatic intraepithelial neoplasia (PanIN) - low grade |
|
Pancreas |
14.3 - 62.5 |
|
| [not specified]-Krastm4.1Bbd | Pancreas pancreatic intraepithelial neoplasia (PanIN) - low grade |
|
Pancreas |
60 - 87.5 |
|
| [not specified]-Krastm4Bbd/+ Tg(Cela1-tTA)#Eps Tg(tetO-cre)3Jig | Pancreas pancreatic intraepithelial neoplasia (PanIN) - low grade |
|
Pancreas |
0 - 30 |
|
| B6;129-Krastm4.1Bbd/+ | Pituitary gland - Anterior adenocarcinoma | Pituitary gland - Anterior |
0 |
||
| B6;129-Krastm4.1Bbd | Pituitary gland - Anterior adenocarcinoma | Pituitary gland - Anterior |
0 - 20 |
||
| B6;129-Krastm4.1Bbd/+ | (Unspecified organ) adenocarcinoma | (Unspecified organ) |
0 - 36 |
||
| B6;129-Krastm4.1Bbd | (Unspecified organ) adenocarcinoma | (Unspecified organ) |
0 - 20 |
||
| B6.129-Krastm4.1Bbd/+ | (Unspecified organ) adenocarcinoma | (Unspecified organ) |
0 - 17 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | (Unspecified organ) adenocarcinoma | (Unspecified organ) |
0 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | (Unspecified organ) adenocarcinoma | (Unspecified organ) |
0 - 20 |
||
| B6;129-Krastm4.1Bbd/+ | (Unspecified organ) adenoma | (Unspecified organ) |
13 - 36 |
||
| B6;129-Krastm4.1Bbd | (Unspecified organ) adenoma | (Unspecified organ) |
0 |
||
| B6.129-Krastm4.1Bbd/+ | (Unspecified organ) adenoma | (Unspecified organ) |
0 - 100 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | (Unspecified organ) adenoma | (Unspecified organ) |
0 - 25 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | (Unspecified organ) adenoma | (Unspecified organ) |
0 - 100 |
||
| B6;129-Krastm4.1Bbd/+ | (Unspecified organ) angiosarcoma | (Unspecified organ) |
0 - 9.1 |
||
| B6;129-Krastm4.1Bbd | (Unspecified organ) angiosarcoma | (Unspecified organ) |
0 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | (Unspecified organ) angiosarcoma | (Unspecified organ) |
78 - 100 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | (Unspecified organ) angiosarcoma | Heart |
0 - 22 |
||
| B6;129 | (Unspecified organ) squamous cell carcinoma | (Unspecified organ) |
0 - 25 |
||
| B6;129-Krastm4.1Bbd/+ | (Unspecified organ) tumor | (Unspecified organ) |
82 - 100 |
||
| B6;129-Krastm4.1Bbd | (Unspecified organ) tumor | (Unspecified organ) |
71 - 80 |
||
| B6;129 | (Unspecified organ) tumor | (Unspecified organ) |
0 - 75 |
||
| B6.129-Krastm4.1Bbd/+ | (Unspecified organ) tumor | (Unspecified organ) |
100 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd/+ | (Unspecified organ) tumor | (Unspecified organ) |
0 - 50 |
||
| 129S2/SvPasCrl-Krastm4.1Bbd | (Unspecified organ) tumor | (Unspecified organ) |
40 - 100 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd | (Unspecified organ) tumor | (Unspecified organ) |
100 |
||
| [not specified]-Cdkn2atm1Rdp Krastm4.1Bbd/+ | (Unspecified organ) tumor | (Unspecified organ) |
100 |
||
| [not specified]-Krastm4.1Bbd/+ Trp53tm1Brd | (Unspecified organ) tumor | (Unspecified organ) |
100 |