Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein as an apoptotic milk factor in mammary gland involution

BACKGROUND: The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. However, little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution. RESULTS: We show the molecular basis by which alpha-lactalbumin (LALBA), a secreted milk protein, is absent in Cape fur seals and demonstrate an apoptotic function for LALBA when exposed to mammary cells. CONCLUSION: We propose that apoptosis does not occur in fur seal mammary glands due to lack of LALBA in fur seal milk, allowing evasion of involution during a foraging trip. Our work identifies LALBA as a milk factor that feeds back on the mammary gland to regulate involution.