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Journal of Virology, October 1999, p. 8669-8676, Vol. 73, No. 10
0022-538X/99/$04.00+0

Transcription Originating in the Long Terminal Repeats of the Endogenous Mouse Mammary Tumor Virus MTV-3 Is Activated in Stat5a-Null Mice and Picks Up Hitchhiking Exons

Svetlana S. Stegalkina, Annamaria Guerrero, Katherine D. Walton, Xiuwen Liu, Gertraud W. Robinson, and Lothar Hennighausen^*

Laboratory of Genetics and Physiology, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 16 June 1999/Accepted 18 June 1999

The enhancer within the long terminal repeats (LTRs) of acquired somatic mouse mammary tumor viruses (MMTV) can activate juxtaposed genes and induce mammary tumors. In contrast, germ line proviral MMTV genomes are integrated in the host genome and considered to be genetically confined transcription units. Here we demonstrate that transcription initiated in an MMTV provirus proceeds into flanking host sequences. We discovered multiple polyadenylated transcripts which are induced in Stat5a null mice. These range from 1.5 kb to more than 8 kb and are specifically expressed in mammary tissue from pregnant and lactating mice from the 129 but not C57BL/6 strain. The RNAs emanate from both LTRs of the endogenous MTV-3 provirus on chromosome 11 and proceed at least 10 kb into the juxtaposed genomic territory. Transcripts originating in the 5' LTR splice from the native splice site within the MMTV envelope gene into at least six exons, three of which contain functional internal splice sites. The combination of alternative splicing and the use of several polyadenylation sites ensure the generation of multiple transcripts. To date no significant open reading frame has been discovered. Furthermore, we demonstrate that transcription from the MMTV 5' LTR is highly active in the absence of Stat5a, a transcription factor that had been shown previously to be required for transcription from the MMTV LTR.

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^* Corresponding author. Mailing address: Laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bldg. 8, Rm. 101, Bethesda, MD 20892. Phone: (301) 496-2716. Fax: (301) 480-7312. E-mail: mammary{at}nih.gov.

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Journal of Virology, October 1999, p. 8669-8676, Vol. 73, No. 10
0022-538X/99/$04.00+0

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