Outline: 

During lactation, the lactating murine mammary gland epithelium undergoes morphological changes which may strongly challenge epithelial barrier properties and regulation of milk composition. Aim of our study was the molecular analysis of tight junctions in native lactating murine mammary gland epithelium.

Methods: 

Mammary gland tissue specimens from lactating control mice and animals after a 20 h interruption of suckling were prepared, and histological analyses were performed by light and electron microscopy. Expression of TJ proteins was detected by PCR, Western blotting, and confocal laser-scanning immunofluorescence microscopy.

Results: 

20 h interruption of suckling resulted in a marked accumulation of milk in mammary glands, and an increase of alveolar size without effects on inflammatory indicators. PCR and Western blots showed signals for occludin, claudin-1 to -5, -7, -8, -15, and -16. After 20 h accumulation of milk, expression of two TJ proteins involved in cation transport, claudin-2 and -16, were reduced, whereas the sealing TJ proteins claudin-1 and -3 were markedly increased. Real-time PCR validated increased transcripts of claudin-1 and -3. No significant changes were observed for other tight junction proteins.

Conclusion: 

Discontinuation of suckling leads to an extension of mammary glands, paralleled by an induction of claudin-1 and -3, and a decrease of claudin-2 and -16. This counter-regulation of sealing claudins with permeability-mediating claudins indicates a physiological process of a sealing of the TJ against a back-leak of solutes and ions from the alveolar lumen, contributing to composition of milk during lactation.