Production of transgenic rats was not as successful as that reported with mouse systems. Only 7% (7/105) and 14% (6/42) offspring from MMTV-c-erbB-2 and MMTV-TGF alpha microinjected eggs, respectively, carried transgenes. Copy number varied from less than 1 to 50 copies, with transmission to the F1 generation indicating that four founder rats were mosaic.
No tumours appeared in the mammary glands of virgin females of either line. Various pathologies (see below) were however reported in multiparous rats, as has been reported previously for transgenes under control of the MMTV-LTR. Only a single ductal hyperplasia and a small area of fibroadenoma were seen in control non-transgenic rats of similar age and reproductive history.
MMTV-c-erbB-2 transgenics: 23 multiparous females were studied and all showed weak transgene staining in mid-pregnant mammary glands. Eighteen exhibited hyperplasia; four had cystic expansion; 15 had fibroadenoma; three had papillary adenoma; three had DCIS and two had carcinoma. All lesions exhibited staining for c-erbB-2 and this was particularly strong in the cystic expansions and the carcinomas.
MMTV-TGF-alpha transgenics: 29 multiparous females were studied and 11 developed large, solid, palpable lumps in the mammary gland after five or more pregnancies. The lumps grew up to 5 cm in diameter, always appeared on the 10th or 11th day of pregnancy and regressed the day before birth of offspring, the animals then lactated normally. Lumps reappeared more severely on subsequent pregnancies and other lesions were seen, including: fibroma (1), papillary ductal adenoma (3), lactating adenoma (2), ductal carcinoma in situ (4) and carcinoma (2).