A Whey acidic protein promoter (Mouse)/HRAS gene (Human) Transgenic Mutation

Summary
The 3 RAS oncogenes, HRAS, KRAS, and NRAS, encode 21-kD proteins called p21s. Mutated HRAS genes are found in a variety of human tumors and are powerful transforming agents in vitro. This transgenic line carries a Gly to Val mutation at codon 12 and was originally derived from T24 human bladder carcinoma cells. The mouse whey acidic protein promoter the major protein in rodent milk and is regulated by prolactin and modulated by insulin and hydrocortisone. Therefore HRAS expression is tissue specific and hormone dependent.

Citation
Nielsen LL, Discafani CM, Gurnani M, Tyler RD. 1991. Histopathology of salivary and mammary gland tumors in transgenic mice expressing a human Ha-ras oncogene. Cancer Res. 51:3762-3767.

Nielsen LL, Gurnani M, Catino JJ, Tyler RD. 1995. In wap-ras transgenic mice, tumor phenotype but not cyclophosphamide-sensitivity is affected by genetic background. Anticancer Res. 15:385-392.

Background

Transgene

mouse strain
The transgene integrated into the Y chromosome. These transgenics serve as models for male mammary cancer, ras-mediated solid tumors and the transgene also can be used as a Y-chromosome marker.

Mammary Phenotype

Mammary Gland Phenotype
On the B6,SJL background males develop multiple mammary tumors and salivary gland tumors by one year of age. The salivary tumors are adenocarcinomas arising from serous areas of the submandibular gland. The mammary gland tumors are adenosquamous carcinomas. Microscopic lung metastases were present in 14% of tumor bearing animals.

On the FVB background males develop multiple mammary tumors at 6-8 weeks. The tumors are adenosquamous carcinomas with multiple foci of squamous differentiation or adenocarcinomas containing glandular tissue. There is no metastasis observed.

Controls
The genetic background of JR# 2409 is mixed C57BL/6 x SJL. Normal wildtype siblings or mice from the B6SJLF1/J colony may be used as controls. The B6SJLF1/J mice only provide an approximate genetic match to this B6,SJL background.

The genetic background of JR# 2410 is FVB/N. Normal wildtype siblings or FVB/N mice may be used as controls.

Colony Maintenance
The B6,SJL strain is maintained by homozygous sibling matings.

The FVB strain is maintained by mating a hemizygous male to an FVB female. Hemizygous transgenic males are fertile, hemizygous transgenic females are fertile but do not lactate. Offspring are foster-nursed, often to FVB mice. Transgenic males are crossed back to SJL females. These mice do best on a high fat diet.

Genetic Typing
For information on genotyping this strain, inquire by e-mail at micetech@jax.org or call 1-800-422-MICE.

key words
oncogene, ras, WAP, whey acidic protein, mammary tumor

Originator
Dr. Loretta L. Nielsen
Schering-Plough Research Institute
K15-4945
2015 Galloping Hill Road
Kenilworth, NJ 07033
Phone 908-298-7335
FAX 908-298-7115
Contact:  nielsel@rockvax.rockefeller.edu

Jackson lab ID
B6,SJL-TgN(WapHRAS)69Lln (JR# 2409)

FVB/N-TgN(WapHRAS)69Lln Y (JR# 2410)

Information submitted by
Debbie Krupke (dmk@jax.org), Induced Mutant Resource, The Jackson Laboratory. on November 17, 1995

For inquiries and to place a request for mice, contact the Customer Service Department at 1-800-422-MICE.

contributed March 1996
last update:  December 1998