Characterization of mammary-specific disruptions for Tph1 and Lrp5 during murine lactation

Abstract

Serotonin is a homeostatic regulator of the mammary gland during lactation. The contribution of mammary-derived serotonin to circulating serum serotonin concentrations was previously unknown. We have developed mice with mammary-specific disruptions of tryptophan hydroxylase 1 ( Tph1) or low-density lipoprotein receptor-related protein 5 ( Lrp5) that are induced during late pregnancy and lactation via use of the whey acidic protein ( WAP)- Cre cre-lox system. Our objective was to characterize dams with a lactation- and mammary-specific disruption of Lrp5 ( WAP-Cre ×  Lrp5 ^FL/FL) or Tph1 ( WAP-Cre ×  Tph1 ^FL/FL). Milk yield and pup weights were recorded throughout lactation. Dams were euthanized on d10 postpartum and mammary glands and duodenal tissue were harvested. WAP-Cre ×  Lrp5 ^FL/FL dams had elevated serotonin concentrations in both the mammary gland and circulation compared to controls. In contrast, WAP-Cre ×  Tph1 ^FL/FL dams had decreased mammary gland and serum serotonin concentrations compared to controls. Alveolar morphology, milk yield, and pup weights were similar. Mammary-derived serotonin makes a significant contribution to circulating serotonin concentrations during lactation, with no effect on milk yield or alveolar morphology. These transgenic models can and should be confidently used in future lactation studies to further elucidate the contribution of serotonin to the maintenance of lactation.