Reference SummarySinn E, Cell 1987 May 22;49(4):465-75

Title

Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo.

Authors

Sinn E; Muller W; Pattengale P; Tepler I; Wallace R; Leder P

Journal

Cell

Volume

49

Issue

4

Year

1987

Pages

465-75

Abstract

We have derived and mated separate strains of transgenic mice that carry either the v-Ha-ras or the c-myc gene driven by the mouse mammary tumor virus (MMTV) promoter/enhancer. Mice carrying the MMTV/v-Ha-ras transgene manifest two distinct disturbances of cell growth. The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene. The second involves the focal development of malignancies of mammary, salivary, and lymphoid tissue and likely requires additional somatic events. When the MMTV/v-Ha-ras and MMTV/c-myc strains are crossed to yield hybrid mice, their joint action results in a dramatic and synergistic acceleration of tumor formation. Since these tumors arise stochastically and are apparently monoclonal in origin, additional somatic events appear necessary for their full malignant progression, even in the presence of activated v-Ha-ras and c-myc transgenes.

Links

J:46454 – MGI References
3032456 – National Library of Medicine/PubMed

Strain Notes

Strain Note
CD-1;B6-Tg(MMTV-Myc)141-3Led Expression of the "MMTV -cmyc" transgene was reported to be expressed in the mammary glands and salivary glands of these mice.
CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Expression of the "MMTV-cmyc" transgene was reported to not be detected in the mammary glands, Harderian glands, thymus, lungs, and liver of these mice.
Expression of the "MMTV-cmyc" transgene was reported to not be detected in the thymus and liver of these mice.
Expression of the "MMTV-cmyc" transgene was reported to not be detected in the thymus, kidney, liver, skeletal muscle, heart, brain, and pancreas of these mice.
Expression of the "MMTVv-Ha-ras" transgene was reported to not be detected in the Harderian glands, thymus, and liver of these mice.
Expression of the "MMTVv-Ha-ras" transgene was reported to not be detected in the mammary glands, Harderian glands, thymus, lungs and liver of these mice.
Expression of the "MMTVv-Ha-ras" transgene was reported to not be detected in the salivary glands, Harderian glands, thymus, ovaries, kidneys, liver, skeletal muscle, small intestine, adrenal glands, heart, brain and pancreas of these mice.
The "MMTV-cmyc" transgene was reported to be highly expressed in the mammary glands, expressed in the salivary glands and Harderian glands, and slightly expressed in the spleen, lungs, ovaries, small intestine and adrenal glands of these mice.
The "MMTV-cmyc" transgene was reported to be highly expressed in the spleen and seminal vesicles and slightly expressed in the salivary glands of these mice.
The "MMTVv-Ha-ras" transgene was reported to be highly expressed in the mammary glands and expressed in the spleen and lungs of these mice.
The "MMTVv-Ha-ras" transgene was reported to be highly expressed in the spleen and slightly expressed in the salivary glands of these mice.
CD-1;B6-Tg(MMTV-vHaras)SH1Led Expression of the "MMTVv-Ha-ras" transgene was reported to not be detected in the small intestine, adrenal glands, heart, brain and pancreas of these mice.
The transgenic construct was reported to be highly expressed in the mammary glands and salivary glands, expressed in the Harderian glands, thymus and spleen, slightly expressed in the lungs, ovaries and kidneys, and little or no expression was reported to have been observed in the liver and skeletal muscle of these mice.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1;B6-Tg(MMTV-vHaras)SH1Led Eye - Harderian gland hyperplasia Eye - Harderian gland

observed - 20

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Eye - Harderian gland hyperplasia Eye - Harderian gland

observed

CD-1;B6-Tg(MMTV-vHaras)SQ1Led Eye - Harderian gland hyperplasia Eye - Harderian gland

14

CD-1;B6-Tg(MMTV-vHaras)SH1Led Leukocyte - Lymphoblast lymphoma - lymphoblastic Leukocyte - Lymphoblast

0 - observed

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

9.5

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Leukocyte - Lymphocyte - B-lymphocyte lymphoma - immunoblastic Leukocyte - Lymphocyte - B-lymphocyte

observed - 29

CD-1;B6-Tg(MMTV-Myc)141-3Led Leukocyte lymphoma Leukocyte

0

CD-1;B6-Tg(MMTV-Myc)141-3Led Mammary gland adenocarcinoma Mammary gland

0 - 50

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Mammary gland adenocarcinoma Mammary gland

high - 86

CD-1;B6-Tg(MMTV-vHaras)SH1Led Mammary gland adenocarcinoma Mammary gland

observed - 77

CD-1;B6-Tg(MMTV-vHaras)SH1Led Salivary gland - Parotid adenocarcinoma Salivary gland - Parotid

observed - 17

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Salivary gland - Parotid adenocarcinoma Salivary gland - Parotid

19

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Salivary gland adenocarcinoma Salivary gland

observed

CD-1;B6-Tg(MMTV-Myc)141-3Led Salivary gland tumor Salivary gland

0

CD-1;B6-Tg(MMTV-Myc)141-3Led Tg(MMTV-vHaras)SH1Led Seminal vesicle tumor Seminal vesicle

observed

CD-1;B6 (Unspecified organ) tumor (Unspecified organ)

0

CD-1;B6-Tg(MMTV-Myc)141-3Led (Unspecified organ) tumor (Unspecified organ)

0