Showing papers by "Richard Lathe published in 1989"

Expression of human anti-hemophilic factor-ix in the milk of transgenic sheep

Abstract: Transgenic livestock may prove useful for the large scale production of valuable proteins. By targeting expression to the mammary gland these proteins could be harvested from milk. To this end, we have designed a hybrid gene to direct the synthesis of human anti-hemophilic factor IX to the mammary gland, and introduced it into sheep. Two transgenic ewes, each carrying about 10 copies of the foreign gene, have been analysed for expression. Both animals express human factor IX RNA in the mammary gland and secrete the corresponding protein into their milk.

Breast cancer protein PS2 synthesis in mammary gland of transgenic mice and secretion into milk.

Abstract: PS2, a small estrogen-inducible secretory polypeptide with structural analogies to a growth factor, is produced by approximately 50% of human breast tumors. The function of PS2 is, however, unknown. To determine whether PS2 may play an autocrine role in the development of mammary tumors we constructed transgenic mice bearing fusion constructs designed to direct the expression of human PS2 in the lactating mammary gland under the control of the whey acidic protein (WAP) promoter. Mouse lines bearing the genomic PS2 gene under the control of the WAP promoter region (WAP-PS2-2) failed to express the transgene. However, mice harboring the fusion construct WAP-PS2-1, in which the PS2 coding sequence is inserted into the 5' untranslated region of the complete WAP gene, were observed to express the transgene. Expression was restricted to the secretory epithelium of the mammary gland during lactation, and PS2 protein was secreted into the milk. Nevertheless, no mammary gland dysplasia was observed, and PS2 expression had no discernable effect upon the physiology and/or development of the suckling young or the transgenic mother.

Recombinant Proteins of Therapeutic Interest Expressed by Lymphoid Cell Lines Derived from Transgenic Mice

Abstract: As a new approach to produce human proteins of therapeutic interest we have derived lymphoid cell lines expressing such proteins from transgenic mice, either by generating trans-hybridomas by cell fusion in vitro or by onc gene-mediated immortalisation in vivo of transgenic lymphocytes. The latter procedure could be applied to different cell types for the expression of proteins that require tissue-specific modifications.

The E2 trans-activating protein of bovine papillomavirus type 1 (BPV1) is serine-phosphorylated in vivo.

Abstract: The E2 open reading frame of bovine papillomavirus 1 (BPV1) encodes both positive and negative transcriptional regulatory factors. The full-length E2 gene polypeptide is a strong transcriptional transactivator that acts on enhancers within the papillomavirus long control region (LCR), and two shorter E2 proteins function as transcription repressors. A vaccinia recombinant virus harboring the full length E2 coding sequence of BPV1 directs the synthesis of a 48 kD phosphoprotein with specific DNA binding activity. We show that in BPV1-transformed cells the full-length transactivator is a phosphoprotein, whereas truncated E2 proteins were not detectably phosphorylated.

Towards a breast cancer vaccine

Abstract: Vaccinia virus (VV), a typical poxvirus used extensively to control and eradicate smallpox, is now widely used as a live recombinant vector for the expression of foreign antigens. We have used a rat model experimental system to explore the possibility of using live VV recombinants in anti-tumor immunization and we discuss the possibility of extending this approach to breast cancer