A colostrum trypsin inhibitor gene expressed in the Cape fur seal mammary gland during lactation

• Published in: Gene
• Main Authors: Pharo, Elizabeth A., Cane, Kylie N., Mccoey, Julia, Buckle, Ashley M., Oosthuizen, W. H., Guinet, Christophe, Arnould, John P. Y.
• Other Authors: School of BioSciences Melbourne, Faculty of Science Melbourne, University of Melbourne-University of Melbourne, Cooperative Research Centre for Innovative Dairy Products, Monash University Clayton, Oceans and Coasts Research, Department of Environmental Affairs, Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), Institut National de la Recherche Agronomique (INRA)-La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), School of Life and Environmental Sciences, Deakin University Burwood
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2016
• Subjects: Pinniped; Kunitz; BPTI; Protease; Walrus; Milk; [SDE]Environmental Sciences; Pacific; Weddell; Weddell Seal; walrus*
• Online Access: https://hal.science/hal-01294536; https://doi.org/10.1016/j.gene.2015.11.042

International audience The colostrum trypsin inhibitor (CTI) gene and transcript were cloned from the Cape fur seal mammary gland and CTI identified by in silico analysis of the Pacific walrus and polar bear genomes (Order Carnivora), and in marine and terrestrial mammals of the Orders Cetartiodactyla (yak, whales, camel) and Perissodactyla (white rhinoceros). Unexpectedly, Weddell seal CTI was predicted to be a pseudogene. Cape fur seal CTI was expressed in the mammary gland of a pregnant multiparous seal, but not in a seal in its first pregnancy. While bovine CTI is expressed for 24–48 h postpartum (pp) and secreted in colostrum only, Cape fur seal CTI was detected for at least 2–3 months pp while the mother was suckling its young on-shore. Furthermore, CTI was expressed in the mammary gland of only one of the lactating seals that was foraging at-sea. The expression of β-casein (CSN2) and β-lactoglobulin II (LGB2), but not CTI in the second lactating seal foraging at-sea suggested that CTI may be intermittently expressed during lactation. Cape fur seal and walrus CTI encode putative small, secreted, N-glycosylated proteins with a single Kunitz/bovine pancreatic trypsin inhibitor (BPTI) domain indicative of serine protease inhibition. Mature Cape fur seal CTI shares 92% sequence identity with Pacific walrus CTI, but only 35% identity with BPTI. Structural homology modelling of Cape fur seal CTI and Pacific walrus trypsin based on the model of the second Kunitz domain of human tissue factor pathway inhibitor (TFPI) and porcine trypsin (Protein Data Bank: 1TFX) confirmed that CTI inhibits trypsin in a canonical fashion. Therefore, pinniped CTI may be critical for preventing the proteolytic degradation of immunoglobulins that are passively transferred from mother to young via colostrum and milk.