Reference SummaryWeissenberger J, Oncogene 1997 May 1;14(17):2005-13
Title |
Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. | ||||||||
Authors |
Weissenberger J; Steinbach JP; Malin G; Spada S; Rulicke T; Aguzzi A | ||||||||
Journal |
Oncogene | ||||||||
Volume |
14 | ||||||||
Issue |
17 | ||||||||
Year |
1997 | ||||||||
Pages |
2005-13 | ||||||||
Abstract |
We have generated a transgenic mouse model for astrocytoma by expressing the v-src kinase under control of the glial fibrillary acidic protein (GFAP) gene regulatory elements in astrocytes. Abnormal astrogliosis was observed in all transgenic animals already at 2 weeks postnatally, frequently followed by the development of dysplastic changes. Later, small proliferative foci arose, and overt astrocytoma developed in the brain and spinal cord in 14.4% of mice after a follow up time of 65 weeks. While early lesions were histologically consistent with low-grade astrocytoma, at later stages most tumors were highly mitotic and frankly malignant. Vascular endothelial growth factor (VEGF) was expressed by tumor cells already at early stages, suggesting induction by v-src, and it was most pronounced in pseudopalisading cells surrounding necrotic areas, implying additional upregulation by hypoxia. In larger lesions, mitotic activity and expression of flk-1, the cognate receptor of VEGF were induced in endothelial cells. Therefore, end-stage tumors mimicked the morphological and molecular characteristics of human glioblastoma multiforme. Time course and stochastic nature of the process indicate that v-src did not suffice for malignant transformation, and that astrocytomas were the result of a multistep process necessitating co-operation of additional genetic events. | ||||||||
Links |
J:40335 – MGI References 9160879 – National Library of Medicine/PubMed |
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Strain Notes
|
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
B6;C3-Tg(GFAP-SRC)1Aag | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
4.9 |
||
B6;C3-Tg(GFAP-SRC)2Aag | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
23 |
||
129/Sv | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
0 |
||
C57BL/6 | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
0 |
||
B6;C3-Tg(GFAP-SRC)3Aag | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
0 |
||
B6;C3-Tg(GFAP-SRC)1Aag | CNS - Brain - Astrocyte dysplasia | CNS - Brain - Astrocyte |
16 |
||
B6;C3-Tg(GFAP-SRC)2Aag | CNS - Brain - Astrocyte dysplasia | CNS - Brain - Astrocyte |
27 |
||
B6;C3-Tg(GFAP-SRC)3Aag | CNS - Brain - Astrocyte dysplasia | CNS - Brain - Astrocyte |
0 |
||
B6;C3-Tg(GFAP-SRC)1Aag | CNS - Brain - Astrocyte preneoplastic lesion | CNS - Brain - Astrocyte |
11 |
||
B6;C3-Tg(GFAP-SRC)2Aag | CNS - Brain - Astrocyte preneoplastic lesion | CNS - Brain - Astrocyte |
17 |
||
B6;C3-Tg(GFAP-SRC)3Aag | CNS - Brain - Astrocyte preneoplastic lesion | CNS - Brain - Astrocyte |
0 |
||
B6;C3-Tg(GFAP-SRC)2Aag | PNS - Schwann cell schwannoma | PNS - Schwann cell |
5.8 |