title: Differential expression of claudin 1, 3, and 4 during normal mammary gland development in the mouse.
abstract: The claudins are a family of tight junction proteins that display varied tissue distribution and preferential specificity. We recently identified by microarray analysis, members of this family, particularly claudin 1 (cldn1), as highly upregulated genes in the mouse mammary gland during early involution. Gene expression was confirmed by immunohistochemistry and real-time PCR. We then examined gene and protein expression throughout normal mammary gland development. The cldn3 gene showed a steady increase in expression from pregnancy to involution, while cldn1 and cldn4 gene expression increased during pregnancy, but decreased sharply by D10 of lactation, and once again was significantly increased by D1 of involution (P < 0.001 for both genes). The different patterns of gene expression observed between cldn3, and cldn1, and 4 suggest that different family members may be functionally important at different times during mouse mammary gland development. All three genes exhibited a high level of expression at day 1 (D1) of involution, followed by a dramatic decrease in gene expression to day 10 of involution. Immunostaining with the cldn3 antibody showed intense staining of epithelial cells; however, a lesser degree of staining was evident with the cldn1 antibody. In addition to the lateral staining of epithelial cells, basal staining was evident at D1 and D2 of involution and cytoplasmic staining was evident during lactation. Since claudins are known to play a role as tight junction proteins, lateral and basal staining may suggest a role in other functions such as vesicle trafficking or remodeling of tight junctions at different stages of mammary gland development. Cldn1 and 3 antibodies also stained epithelial cells in mouse mammary tumors. In summary, cldn1, 3, and 4 are differentially expressed in the mammary gland during pregnancy, lactation, and involution, suggesting different roles for these proteins at different stages of mammary gland function. In addition, cldn1 and cldn3 are detected in mammary tumors and the wide distribution of cldn3 in particular, suggest specific roles for these proteins in mammary tumorigenesis.
authors.affiliation: Department of Pathology and Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Anne A A
authors.initials: AA
authors.lastname: Blanchard
authors.forename: Peter H
authors.initials: PH
authors.lastname: Watson
authors.forename: Robert P C
authors.initials: RP
authors.lastname: Shiu
authors.forename: Etienne
authors.initials: E
authors.lastname: Leygue
authors.forename: Andreea
authors.initials: A
authors.lastname: Nistor
authors.forename: Paul
authors.initials: P
authors.lastname: Wong
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Myal
mesh_terms: D000818:Animals; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D005260:Female; D007150:Immunohistochemistry; D007774:Lactation; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000502:physiology*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D011247:Pregnancy; D046888:Tissue Array Analysis
chemical_list: D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; C568113:Cldn1 protein, mouse; C568123:Cldn3 protein, mouse; C568158:Cldn4 protein, mouse; D008565:Membrane Proteins