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Bovine Muc1 is a highly polymorphic gene encoding an extensively glycosylated mucin that binds bacteria

L. Sando^*,,1, R. Pearson^*,,1, C. Gray^*,,1,2, P. Parker, R. Hawken^*,, P. C. Thomson^,, J. R. S. Meadows^*,, K. Kongsuwan^*,, S. Smith and R. L. Tellam^*,,3

^* CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Rd., St. Lucia, QLD 4067, Australia
Co-operative Research Centre for Innovative Dairy Products (CRC-IDP), 84 William Street, Melbourne, Victoria 3000, Australia
Deakin University, 225 Burwood Hwy, Burwood, Victoria 3151, Australia
Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), University of Sydney, PMB3 Camden, New South Wales 2570, Australia

³ Corresponding author: ross.tellam{at}csiro.au

The bovine Muc1 protein is synthesized by mammary epithelial cells and shed into milk as an integral component of the milk fat globule membrane; however, the structure and functions of this mucin, particularly in relation to lactation, are poorly defined. The objectives of this investigation were to investigate the Muc1 gene and protein structures in the context of lactation and to test the hypothesis that Muc1 has a role in innate immune defense. Polymerase chain reaction analysis of genomic DNA from 630 cattle revealed extensive polymorphism in the variable number of tandem repeats (VNTR) in the bovine Muc1 gene. Nine allelic variants spanning 7 to 23 VNTR units, each encoding 20 AA, were identified. Three alleles, containing 11, 14, and 16 VNTR units, respectively, were predominant. In addition, a polymorphism in one of the VNTR units has the potential to introduce a unique site for N-linked glycosylation. Statistical analysis indicated weak associations between the VNTR alleles and milk protein and fat percentages in a progeny-tested population of Holstein-Friesian dairy cattle. No association with somatic cell count could be demonstrated. Bovine Muc1 was purified from milk fat globule membranes and characterized. The protein was highly glycosylated, primarily with O-linked sialylated T-antigen [Neu5Ac(2–3)-Gal(β1–3)-GalNAc1] and, to a lesser extent, with N-linked oligosaccharides, which together accounted for approximately 60% of the apparent mass of Muc1. Purified bovine Muc1 directly bound fluorescently labeled Escherichia coli BioParticles (Invitrogen, Mount Waverley, Australia) and inhibited their binding to bovine mammary epithelial cells grown in vitro. It was also demonstrated that the expression of Muc1 mRNA in bovine mammary epithelial cells was markedly upregulated by lipopolysaccharide. Muc1 may be a pattern recognition protein that has the capacity to sequester bacteria and prevent their attachment to epithelial surfaces by immobilizing and subsequently shedding Muc1-bound bacteria from the cell surface. It was concluded that bovine Muc1 is probably an inducible innate immune effector and an important component of the first line of defense against bacterial invasion of epithelial surfaces, particularly mammary epithelial surfaces and the neonatal gut.

Key Words: Muc1 • mucin • polymorphism • innate immunity