Ectopic expression of tethered human follicle-stimulating hormone (hFSH) gene in transgenic mice.
To determine whether the mammary gland can be used to secrete large quantities of a bioactive heterodimeric protein into milk, we used a bovine beta-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.
Kim
Myoung Ok
MO
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu, 702-701, Korea.
Kim
Sung Hyun
SH
Lee
Sang Ryeul
SR
Shin
Mi Jung
MJ
Min
Kwan Sik
KS
Lee
Dong Beom
DB
Lee
Sung Won
SW
Kim
Kil Soo
KS
Kim
Sun Jung
SJ
Ryoo
Zae Young
ZY
D000818:Animals; D001483:Base Sequence; D001772:Blood Cell Count; D002364:Caseins / Q000235:genetics; D002417:Cattle; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008892:Milk / Q000378:metabolism; D010053:Ovary / Q000033:anatomy & histology; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002364:Caseins; D017931:DNA Primers; D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins