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Hum. Reprod. Advance Access published online on April 22, 2004
Human Reproduction, doi:10.1093/humrep/deh297
© 2004 by European Society of Human Reproduction and Embryology
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Received February 9, 2004
Accepted April 8, 2004

Article

Transgenic mice as a model to study the regulation of human transferrin expression in Sertoli cells

C. Lécureuil 1, M.C. Saleh 2, I. Fontaine 1, B. Baron 2, M.M. Zakin 2, F. Guillou 1*

1 UMR 6175 Institut National de la Recherche Agronomique, Centre National de Recherche Scientifique, Université de Tours, Haras Nationaux ‘Physiologie de la Reproduction et des Comportements’, 37380 Nouzilly, France
2 Unité d’Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France

* To whom correspondence should be addressed. E-mail: guillou{at}tours.inra.fr.


  Abstract

BACKGROUND: Understanding the regulation of proteins secreted by human Sertoli cells is important for identifying the causes of infertility in men. However, experiments with Sertoli cells purified from healthy testes are difficult to perform, for obvious ethical reasons. Therefore, experiments with transgenic mouse models could provide an alternative approach to study the function and regulation of a human gene in Sertoli cells. METHODS: To validate this approach, transgenic mice were generated using phage P1 containing an 80 kbp insert encompassing the complete human transferrin (hTf) gene. The expression pattern of hTf in the mouse background was analysed by isolating Sertoli cells from transgenic mice and comparing the regulation of the human and mouse Tf genes by hormones, retinoids and a cytokine in vitro. RESULTS: The hTf gene in transgenic mice shows a tissue-specific expression pattern that mimics the pattern observed in the human. In Sertoli cell cultures, FSH, insulin, retinol or tumour necrosis factor-{alpha} (TNF-{alpha}) stimulated hTf secretion, while testosterone alone had no effect. A combination of FSH, insulin, retinol and testosterone or a combination of TNF-{alpha} and retinol stimulated hTf secretion, but no additive effect was observed. CONCLUSION: Besides their well-known advantages, transgenic mice seem to be useful models to recapitulate the normal regulation of a human gene.

Key words: Key words: PAC/regulation/Sertoli/transferrin/transgenic mice


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