Reference SummaryCastillo A, Cancer Res 2007 Nov 1;67(21):10138-47
Title |
Overexpression of Eg5 causes genomic instability and tumor formation in mice. |
Authors |
Castillo A; Morse HC 3rd; Godfrey VL; Naeem R; Justice MJ |
Journal |
Cancer Res |
Volume |
67 |
Issue |
21 |
Year |
2007 |
Pages |
10138-47 |
Abstract |
Proper chromosome segregation in eukaryotes is driven by a complex superstructure called the mitotic spindle. Assembly, maintenance, and function of the spindle depend on centrosome migration, organization of microtubule arrays, and force generation by microtubule motors. Spindle pole migration and elongation are controlled by the unique balance of forces generated by antagonistic molecular motors that act upon microtubules of the mitotic spindle. Defects in components of this complex structure have been shown to lead to chromosome missegregation and genomic instability. Here, we show that overexpression of Eg5, a member of the Bim-C class of kinesin-related proteins, leads to disruption of normal spindle development, as we observe both monopolar and multipolar spindles in Eg5 transgenic mice. Our findings show that perturbation of the mitotic spindle leads to chromosomal missegregation and the accumulation of tetraploid cells. Aging of these mice revealed a higher incidence of tumor formation with a mixed array of tumor types appearing in mice ages 3 to 30 months with the mean age of 20 months. Analysis of the tumors revealed widespread aneuploidy and genetic instability, both hallmarks of nearly all solid tumors. Together with previous findings, our results indicate that Eg5 overexpression disrupts the unique balance of forces associated with normal spindle assembly and function, and thereby leads to the development of spindle defects, genetic instability, and tumors. |
Links |
J:127104 – MGI References 17974955 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Blood vessel hemangioma | Spleen |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma - follicular | Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte - Lymphocyte - B-lymphocyte - Plasma cell plasmacytoma | Leukocyte - Lymphocyte - B-lymphocyte - Plasma cell |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte - Lymphocyte - B-lymphocyte lymphoma - splenic marginal zone | Leukocyte - Lymphocyte - B-lymphocyte |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte - Megakaryocyte leukemia | Leukocyte - Megakaryocyte |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte - Myelocyte (Granulocyte) - Basophil - Mast cell mastocytoma | Leukocyte - Myelocyte (Granulocyte) - Basophil - Mast cell |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte - Myelocyte (Granulocyte) hyperplasia | Spleen |
observed |
||
| FVB/NJ | Leukocyte neoplasia | Leukocyte |
2.0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Leukocyte neoplasia | Leukocyte |
3.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Leukocyte neoplasia | Leukocyte |
2.9 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Leukocyte neoplasia | Leukocyte |
7.1 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Leukocyte neoplasia | Leukocyte |
4.7 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Lung adenocarcinoma | Lung |
observed |
||
| FVB/NJ | Lung tumor | Lung |
2.0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Lung tumor | Lung |
13 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Lung tumor | Lung |
4.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Lung tumor | Lung |
8.6 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Lung tumor | Lung |
7.6 |
||
| FVB/NJ | Lymphoid tissue tumor | Lymphoid tissue |
2.0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Lymphoid tissue tumor | Lymphoid tissue |
3.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Lymphoid tissue tumor | Lymphoid tissue |
4.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Lymphoid tissue tumor | Lymphoid tissue |
10 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Lymphoid tissue tumor | Lymphoid tissue |
6.5 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Mammary gland adenocarcinoma | Mammary gland |
3.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Mammary gland adenocarcinoma | Mammary gland |
observed |
||
| FVB/NJ | Mammary gland tumor | Mammary gland |
2.0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Mammary gland tumor | Mammary gland |
3.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Mammary gland tumor | Mammary gland |
5.7 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Mammary gland tumor | Mammary gland |
7.1 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Mammary gland tumor | Mammary gland |
5.9 |
||
| FVB/NJ | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
3.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
0 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
2.9 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
1.8 |
||
| FVB/NJ | Ovary - Germ cell teratoma | Ovary - Germ cell |
0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Ovary - Germ cell teratoma | Ovary - Germ cell |
3.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Ovary - Germ cell teratoma | Ovary - Germ cell |
0 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Ovary - Germ cell teratoma | Ovary - Germ cell |
2.9 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Ovary - Germ cell teratoma | Ovary - Germ cell |
1.8 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | PNS - Schwann cell schwannoma | PNS - Schwann cell |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Spleen - Red pulp hyperplasia | Spleen - Red pulp |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | Spleen hyperplasia | Spleen |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | Spleen hyperplasia | Spleen |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | Spleen hyperplasia | Spleen |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Spleen hyperplasia | Spleen |
observed |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | Uterus - Myometrium neoplasia | Uterus - Myometrium |
observed |
||
| FVB/NJ | (Unspecified organ) tumor | (Unspecified organ) |
6.0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | (Unspecified organ) tumor | (Unspecified organ) |
26.7 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | (Unspecified organ) tumor | (Unspecified organ) |
15.7 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | (Unspecified organ) tumor | (Unspecified organ) |
31.4 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | (Unspecified organ) tumor | (Unspecified organ) |
24.1 |
||
| FVB/NJ | (Unspecified organ) tumor - unclassified | (Unspecified organ) |
0 |
||
| FVB/NJ-Tg(Pim1-Eg5)1Jus | (Unspecified organ) tumor - unclassified | (Unspecified organ) |
0 |
||
| FVB/NJ-Tg(Pim1-Eg5)2Jus | (Unspecified organ) tumor - unclassified | (Unspecified organ) |
4.3 |
||
| FVB/NJ-Tg(Pim1-Eg5)3Jus | (Unspecified organ) tumor - unclassified | (Unspecified organ) |
5.7 |
||
| FVB/NJ-Tg(Pim1-Eg5)#Jus | (Unspecified organ) tumor - unclassified | (Unspecified organ) |
4.1 |