Diminished Milk Synthesis in Upstream Stimulatory Factor 2 Null Mice Is Associated With Decreased Circulating Oxytocin and Decreased Mammary Gland Expression of Eukaryotic Initiation Factors 4E and 4G

Previous studies have suggested that upstream stimulatory factors (USFs) regulate genes involved with cell cycle progression. Because of the relationship of USFs to an important oncogene in breast cancer, c-myc, we chose to determine the importance of USF to normal mammary gland development in the mouse. Expression of USF in the mammary gland throughout development demonstrated only modest changes. Mutation of the Usf2 gene was associated with reduced fertility in females, but had no effect on prepartum mammary gland development. However, lactation performance in Usf2−/− females was only half of that observed in Usf2+/+ females, and both lactose and nitrogen were decreased in milk from Usf2−/− dams. This decrease was associated with diminished mammary tissue wet weight and luminal area by d 9 of lactation and with a decreased protein-DNA ratio. This decrease was associated with reduced abundance of the eukaryotic initiation factors eIF4E and eIF4G. Blood oxytocin concentrations on d 9 postpartum were also...