Reference SummaryHusler MR, Transgenic Res 1998 Jul;7(4):253-63

Title

Lactation-induced WAP-SV40 Tag transgene expression in C57BL/6J mice leads to mammary carcinoma.

Authors

Husler MR; Kotopoulis KA; Sundberg JP; Tennent BJ; Kunig SV; Knowles BB

Journal

Transgenic Res

Volume

Issue

Year

1998

Pages

253-63

Abstract

Two transgenic lineages were generated by directing the expression of SV40 T antigen to the mammary gland of inbred C57BL/6J mice using the whey acidic protein (WAP) promoter. In one lineage, WAPTag 1, multiparous female mice developed mammary adenocarcinoma with an average latency period of 13 months. The histopathological phenotype was heterogeneous, tumours occurred in a stochastic fashion, normal tissue was located next to neoplastic tissue, the mammary tumours usually developed and were remarkably similar to that observed in human cases. In addition, male and virgin females developed a poorly differentiated SV40 T antigen-positive soft tissue sarcoma, also at 13 months of age. In the other lineage, WAPTag 3, some parous females developed mammary tumours, but most mice succumbed to osteosarcomas arising from the os petrosum at 5.5 to 6 months of age and on necropsy, renal adenocarcinomas were also found. Appearance of these unexpected tumour types demonstrates the non-specific expression of SV40 Tag under the control of the WAP promoter. The expression of SV40 Tag in mammary glands at different stages of development was also examined, and only actively lactating glands were positive. This suggests that the abundant cyclic synthesis of SV40 Tag associated with pregnancy is required for mammary tumorigenesis in these lineages.

Links

J:53175 – MGI References
9859214 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
C57BL/6J-Tg(WapTAg)1Knw/J	These mice were from The Jackson Laboratory. The "WapTAg" transgene was reported to be expressed in the mammary glands of these mice during lactation, but expression of that transgene was not detected in the mammary glands of parous or virgin mice.
C57BL/6J-Tg(WapTAg)3Knw/J	Expression of the "WapTAg" transgene was reported to not be detected in the mammary glands of these mice. These mice were from The Jackson Laboratory. The "WapTAg" transgene was reported to be expressed in the mammary glands of these mice during lactation, but expression of that transgene was not detected in the mammary glands of virgin mice.

Models
Strain	Model Name	Organ Affected	Frequency
C57BL/6J-Tg(WapTAg)3Knw/J	Bone osteosarcoma	Bone - Skull	observed - 100
C57BL/6J-Tg(WapTAg)3Knw/J	Kidney adenocarcinoma	Kidney	observed
C57BL/6J-Tg(WapTAg)1Knw/J	Mammary gland carcinoma	Mammary gland	0 - 76
C57BL/6J-Tg(WapTAg)3Knw/J	Mammary gland carcinoma	Mammary gland	0 - 37.5
C57BL/6J-Tg(WapTAg)1Knw/J	Mammary gland carcinoma in situ	Mammary gland	observed
C57BL/6J-Tg(WapTAg)3Knw/J	Mammary gland hyperplasia	Mammary gland	0 - observed
C57BL/6J-Tg(WapTAg)1Knw/J	Mammary gland hyperplasia	Mammary gland	0
C57BL/6J-Tg(WapTAg)1Knw/J	Mesodermal cell/mesoblast sarcoma	Mesodermal cell/mesoblast	observed - 100
C57BL/6J-Tg(WapTAg)3Knw/J	Renal pelvis adenocarcinoma	Renal pelvis	observed