ABSTRACT
R-spondin1 (Rspo1) is a member of a secreted protein family which has pleiotropic functions in development and stem cell growth. Rspo1 knock-out mice are sex-reversed, but some remain sub-fertile, so they fail to nurse their pups. A lack of Rspo1 expression in the mammary gland results in an absence of duct side-branching development and defective alveolar formation. The aim of this study was to characterize the phenotypic and molecular alterations of mammary gland due to Rspo1 knock-out. Using the transcriptional profiling of mammary tissues, we identified misregulated genes in the mammary gland of Rspo1 knock-out mice during pregnancy. A stronger expression of mesenchymal markers was observed, without modifications to the structure of mammary epithelial tissue. Mammary epithelial cell immunohistochemical analysis revealed a persistence of virgin markers, which signify a delay in cell differentiation. Moreover, serial transplantation experiments showed that Rspo1 is associated with a regenerative potential of mammary epithelial cell control. Our finding also highlights the negatively regulated expression of Rspo1's partners, Lgr4 and RNF43, in the mammary gland during pregnancy. Moreover, we offer evidence that Tgf-ß signalling is modified in the absence of Rspo1. Taken together, our results show an abrupt halt or delay to mammary development during pregnancy due to the loss of a further differentiated function.
Subject(s)
Mammary Glands, Animal/metabolism , Thrombospondins/metabolism , Animals , Axin Protein/genetics , Axin Protein/metabolism , Epithelium/metabolism , Female , Immunohistochemistry , Mice , Mice, Knockout , Polymerase Chain Reaction , Pregnancy , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/genetics , Signal Transduction/physiology , Thrombospondins/deficiency , Thrombospondins/genetics , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
The Viral Hemorrhagic Septicemia Virus (VHSV) and the Infectious Hematopoietic Necrosis Virus (IHNV) are two rhabdoviruses responsible for serious outbreaks in salmonid farms. To date, little is known about the variability of host response to these viruses. Using gynogenetic clonal lines of rainbow trout exhibiting a wide range of resistance to viral infections, we showed that there was no correlation between the resistance to VHSV and IHNV. We also confirmed the importance of fish weight for its susceptibility to IHNV infection. Finally, using a chimeric recombinant IHNV expressing the VHSV glycoprotein, we showed that the glycoprotein plays a key role in the virulence and in the level of resistance observed in different genetic backgrounds. Taken together, our results provide new prospects for a better understanding of host responses to rhabdovirus infections in salmonids.
