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Journal of Virology, January 1999, p. 368-376, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mammary Gland Expression of Mouse Mammary Tumor Virus Is Regulated by a Novel Element in the Long Terminal Repeat

Wei Qin,1 Tatyana V. Golovkina,1,dagger Tao Peng,1,Dagger Irene Nepomnaschy,2 Valeria Buggiano,2 Isabel Piazzon,2 and Susan R. Ross1,*

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6142,1 and Division of Experimental Medicine, Institute of Hematological Research, Academy of Medicine, Buenos Aires, Argentina2

Received 27 March 1998/Accepted 9 October 1998

Mouse mammary tumor virus (MMTV) infects both lymphoid tissue and lactating mammary gland during its infectious cycle, but some endogenous MMTVs are transcribed only in lymphoid cells. We found a lymphoid cell-specific endogenous MMTV that was converted to a milk-borne, infectious virus through recombination with an exogenously transmitted MMTV. The changed expression pattern correlated with the alteration of a single base pair in the long terminal repeat of the lymphoid cell-specific virus. Transgenic mice with the element from either the milk-borne or lymphoid cell-specific virus upstream of the chloramphenicol acetyltransferase reporter gene showed the same pattern of expression as the virus from which the regulatory sequences were derived. Electrophoretic mobility shift assays with mammary cell extracts showed that the site from the milk-borne virus was preferentially bound by a prolactin-inducible factor that poorly bound the altered site from the lymphoid cell-specific virus. The complex that formed on the milk-borne virus-specific oligonucleotide supershifted with anti-Stat5b antibody. Mice lacking either Stat5a or Stat5b had dramatically reduced levels of MMTV transcripts in mammary gland but not in lymphoid tissue. Thus, a member of the STAT family of transcription factors is involved in the tissue-specific expression of mouse mammary tumor virus in vivo. This is the first example of the involvement of a member of the STAT family of transcription factors in the control of tissue-specific expression.

* Corresponding author. Mailing address: University of Pennsylvania, Room 526 CRB, 415 Curie Blvd., Philadelphia, PA 19104-6142. Phone: (215) 898-9764. Fax: (215) 573-2028. E-mail: rosss{at}mail.med.upenn.edu.

dagger Present address: The Jackson Laboratory, Bar Harbor, ME 04609.

Dagger Present address: The Whitehead Institute, Cambridge, MA 02142.

Journal of Virology, January 1999, p. 368-376, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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