Reference SummarySaitoh A, Oncogene 1990 Aug;5(8):1195-200

Title

Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes.

Authors

Saitoh A; Kimura M; Takahashi R; Yokoyama M; Nomura T; Izawa M; Sekiya T; Nishimura S; Katsuki M

Journal

Oncogene

Volume

5

Issue

8

Year

1990

Pages

1195-200

Abstract

Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice.

Links

J:64968 – MGI References
2202951 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;C-Tg(HRAS)2Jic 1st generation progeny (F2 founder crossed to C57BL/6 mice); 75% C57BL/6.
2nd generation progeny (F2 backcrossed twice to C57BL/6 mice); 87.5% C57BL/6.
Visual Summary Grid

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6CF2-Tg(HRAS)2Jic Blood vessel hemangiosarcoma Spleen

100

B6;C-Tg(HRAS)2Jic Blood vessel hemangiosarcoma Spleen

0 - 10

B6;C-Tg(HRAS)2Jic Blood vessel hemangiosarcoma Skin

0 - 14

B6;C-Tg(HRAS)2Jic Blood vessel hemangiosarcoma Peritoneum - Mesentery

0 - 2.0

B6;C-Tg(HRAS)2Jic Blood vessel hemangiosarcoma Kidney

0 - 2.0

C57BL/6-Tg(HRAS)7Mok Blood vessel hemangiosarcoma Blood vessel

33

B6;C-Tg(HRAS)2Jic Eye - Harderian gland adenocarcinoma Eye - Harderian gland

0 - 8.0

C57BL/6-Tg(HRAS)7Mok Eye - Harderian gland adenocarcinoma Eye - Harderian gland

17

B6;C-Tg(HRAS)2Jic Leukocyte lymphoma Lymph node

0 - 2.0

B6;C-Tg(HRAS)2Jic Leukocyte lymphoma Thymus

0 - 2.0

C57BL/6-Tg(HRAS)7Mok Leukocyte lymphoma Leukocyte

33

B6;C-Tg(HRAS)2Jic Lung adenocarcinoma Lung

0 - 16

C57BL/6-Tg(HRAS)7Mok Lung adenocarcinoma Lung

17

B6;C-Tg(HRAS)2Jic Skin papilloma Skin

0 - 6.0

C57BL/6-Tg(HRAS)7Mok Skin papilloma Skin

0

B6;C-Tg(HRAS)2Jic (Unspecified organ) tumor (Unspecified organ)

0 - 48

B6;C (Unspecified organ) tumor (Unspecified organ)

0

C57BL/6-Tg(HRAS)7Mok (Unspecified organ) tumor (Unspecified organ)

50

C57BL/6 (Unspecified organ) tumor (Unspecified organ)

0