Signal transducer and activator of transcription (Stat5) is a transcription 
factor, which transduces extracellular cytokine and growth-factor signals to the 
nuclei of mammalian cells. As a major mediator of prolactin action, it is 
involved in the regulation of the development, function, and survival of mammary 
epithelial cells. The carboxyl terminal of Stat5 encodes a transactivation 
domain (TAD), which interacts with coactivators and is crucial for the 
transcriptional induction of Stat5 target genes. To study the role of the Stat5 
TAD in mediating Stat5 functions, a carboxy terminally truncated Stat5 variant 
(Stat5Delta750) was directed for expression in the mammary glands of transgenic 
mice by regulatory sequences of the beta-lactoglobulin (BLG) gene. Expression of 
Stat5Delta750 in mammary tissue reduced the rates of cell proliferation at mid 
and late pregnancy. Subsequently, morphological signs of milk secretion upon 
parturition were delayed. In double-transgenic mice, expression of Stat5Delta750 
drastically decreased BLG/luciferase activity during lactation, but did not 
affect the expression and secretion of the endogenous beta-casein or 
alpha-lactalbumin into the milk. Expression of Stat5Delta750 also caused an 
increase in the number of apoptotic cells during mammary involution by a factor 
of 3 relative to control glands. Our data established a role for the Stat5 TAD 
in mediating the effects of Stat5 on mammary development, regulation of milk 
protein gene activity, and cell survival. The full effects of Stat5Delta750 may 
be partially buffered by the expression of endogenous wild-type Stat5 and the 
formation of truncated and wild-type heterodimers.