MMTV-Cre transgenes can adversely affect lactation: considerations for conditional gene deletion in mammary tissue

CRE-loxP-mediated inactivation and activation of genes in mouse mammary epithelium have been widely used to study genetic pathways in normal development and neoplastic transformation in vivo. In 1997, we generated three distinct mouse lines carrying an identical MMTV-Cre transgene (lines A, D, and F). Because the presence of CRE recombinase can adversely affect the physiology of nonmammary cells, we explored whether transgenic females display lactational defects. Whereas dams from line D nurse their pups and display overtly normal mammary development, line A shows some impairment during lactation and females from line F completely fail to nurse their litters. The ability to nurse a litter correlates with the extent of alveolar development and differentiation. This study demonstrates the importance of including appropriate "Cre-only" controls and provides guidelines to avoid problems in data interpretation.