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Molecular and Cellular Biology, September 2004, p. 8037-8047, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.8037-8047.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inactivation of Stat5 in Mouse Mammary Epithelium during Pregnancy Reveals Distinct Functions in Cell Proliferation, Survival, and Differentiation

Yongzhi Cui,1 Greg Riedlinger,1 Keiko Miyoshi,1,2 Wei Tang,1 Cuiling Li,3 Chu-Xia Deng,3 Gertraud W. Robinson,1 and Lothar Hennighausen1*

Laboratory of Genetics and Physiology,1 Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland,3 Department of Biochemistry, School of Dentistry, University of Tokushima, Tokushima, Japan2

Received 14 January 2004/ Returned for modification 19 March 2004/ Accepted 13 June 2004

This study explored the functions of the signal transducers and activators of transcription 5a and 5b (referred to as Stat5 here) during different stages of mouse mammary gland development by using conditional gene inactivation. Mammary gland morphogenesis includes cell specification, proliferation and differentiation during pregnancy, cell survival and maintenance of differentiation throughout lactation, and cell death during involution. Stat5 is activated by prolactin, and its presence is mandatory for the proliferation and differentiation of mammary epithelium during pregnancy. To address the question of whether Stat5 is also necessary for the maintenance and survival of the differentiated epithelium, the two genes were deleted at different time points. The 110-kb Stat5 locus in the mouse was bracketed with loxP sites, and its deletion was accomplished by using two Cre-expressing transgenic lines. Loss of Stat5 prior to pregnancy prevented epithelial proliferation and differentiation. Deletion of Stat5 during pregnancy, after mammary epithelium had entered Stat5-mediated differentiation, resulted in premature cell death, indicating that at this stage epithelial cell proliferation, differentiation, and survival require Stat5.

* Corresponding author. Mailing address: Laboratory of Genetics and Physiology, NIDDK, NIH, Building 8, Room 101, Bethesda, MD 20892-0822. Phone: (301) 496-2716. Fax: (301) 480-7312. E-mail: hennighausen{at}nih.gov.

Molecular and Cellular Biology, September 2004, p. 8037-8047, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.8037-8047.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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