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

Strain Notes

Strain Note
B6;C3-Tg(GFAP-SRC)1Aag The "GFAP-v-src" transgene was reported to be expressed in the brain, brain stem, thalamus, cerebellum, astrocytes, lungs, thymus, spleen, and ovaries, and slightly expressed in the spinal cord, Schwann cells, and testis of these mice.
The wild type allele of the Vegf gene was reported to be expressed in astrocytes of these mice.
B6;C3-Tg(GFAP-SRC)2Aag The "GFAP-v-src" transgene was reported to be expressed in the brain, brain stem, thalamus, cerebellum, astrocytes, lungs, thymus, spleen, and ovaries, and slightly expressed in the spinal cord, Schwann cells, and testis of these mice.
The wild type allele of the Vegf gene was reported to be expressed in the astrocytes of these mice.
B6;C3-Tg(GFAP-SRC)3Aag The "GFAP-v-src" transgene was reported to be expressed in the brain, brain stem, thalamus, cerebellum, astrocytes, lungs, thymus, spleen, and ovaries, and slightly expressed in the spinal cord, Schwann cells, and testis of these mice.
The wild type allele of the Vegf gene was reported to be expressed in astrocytes of these mice.

Models
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