Ectopic expression of tethered human follicle-stimulating hormone (hFSH) gene in transgenic mice

• Published in: Transgenic research 2007-02, Vol.16 (1), p.65-75
• Main Authors: Kim, Myoung Ok, Kim, Sung Hyun, Lee, Sang Ryeul, Shin, Mi Jung, Min, Kwan Sik, Lee, Dong Beom, Lee, Sung Won, Kim, Kil Soo, Kim, Sun Jung, Ryoo, Zae Young
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Biotechnology; Blood Cell Count; Caseins - genetics; Cattle; DNA Primers - genetics; Enzyme-Linked Immunosorbent Assay; Female; Follicle Stimulating Hormone, Human - blood; Follicle Stimulating Hormone, Human - genetics; Follicle Stimulating Hormone, Human - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression; Genetic engineering; Genetic technics; Human FSH; Humans; Immunohistochemistry; Mammary gland; Mammary Glands, Animal - anatomy & histology; Mammary Glands, Animal - metabolism; Methods. Procedures. Technologies; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Milk - metabolism; Ovary - anatomy & histology; Promoter Regions, Genetic; Proteins; Recombinant Proteins - blood; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Transgenic animals and transgenic plants; Transgenic mouse; β-Casein promoter
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1007/s11248-006-9031-5

To determine whether the mammary gland can be used to secrete large quantities of a bioactive heterodimeric protein into milk, we used a bovine β-casein promoter to target and express human follicle-stimulating hormone (hFSH) in the mammary gland into the milk of transgenic mice. We also identified the effects of hFSH leaked into the bloodstream. Transgenic mice produced a high level (up to 300 mIU/ml) of recombinant hFSH in the mammary gland. Human FSH was expressed in the mammary gland and brain, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. In vitro bioactivity was also identified by cyclic AMP (cAMP) assay. The highest activity was showed in the transgenic mice line 11. However, hFSH leaked into the bloodstream was a powerful factor in the generation of breast and ovarian tumors from the transgenic mice line 11. These results suggest that change of endogenous hormones (FSH and progesterone) may affect the morphology and blood cell counts of peripheral blood and, especially, provoke breast and ovarian tumors.