A phenotype survey of 36 mutant mouse strains with gene-targeted defects in glycosyltransferases or glycan-binding proteins

Abstract

The consortium for functional glycomics (CFG) was a large research initiative providing networking and resources for investigators studying the role of glycans and glycan-binding proteins in health and disease. Starting in 2001, six scientific cores were established to generate data, materials and new technologies. By the end of funding in 2011, the mouse phenotype core (MPC) submitted data to a website from the phenotype screen of 36 mutant mouse strains deficient in a gene for either a glycan-binding protein (GBP) or glycosyltransferase (GT). Each mutant strain was allotted three months for analysis and screened by standard phenotype assays used in the fields of immunology, histology, hematology, coagulation, serum chemistry, metabolism and behavior. Twenty of the deficient mouse strains had been studied in other laboratories, and additional tests were performed on these strains to confirm previous observations and discover new data. The CFG constructed 16 new homozygous mutant mouse strains and completed the initial phenotype screen of the majority of these new mutant strains. In total, >300 phenotype changes were observed, but considering the over 100 assays performed on each strain, most of the phenotypes were unchanged. Phenotype differences include abnormal testis morphology in GlcNAcT9- and Siglec-H-deficient mice and lethality in Pomgnt1-deficient mice. The numerous altered phenotypes discovered, along with the consideration of the significant findings of normality, will provide a platform for future characterization to understand the important roles of glycans and GBPs in the mechanisms of health and disease.

Systemic Blockade of Sialylation in Mice with a Global Inhibitor of Sialyltransferases

“…Altered liver enzymes were found in several sialyltransferase-deficient mice (19). We suggest that high levels of serum glycoproteins containing unmasked galactose residues that will be exposed without terminal sialylation may overwhelm the hepatocyte asialoglycoprotein receptor that normally clears these proteins, and the resulting stress may alter liver function.…”

“…Importantly, because of differences in acceptor substrate specificity and gene expression patterns of these related enzymes, cells and tissues display unique sialoside structures, which can have important functional consequences (13)(14)(15). Studies examining sialyltransferase-deficient mice, for instance, have shed light on some of the important biological roles played by sialosides in the immune response (16 -22), brain (23)(24)(25)(26)(27), and blood/liver (19,28).…”

Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation

“…Genetic remodeling of protein glycosylation in mice reveals that glycans play important roles in autoimmune disease and inflammation (36). Conversely, infection and inflammation lead to changes in host glycan structure (37).…”

Competition between Core-2 GlcNAc-transferase and ST6GalNAc-transferase Regulates the Synthesis of the Leukocyte Selectin Ligand on Human P-selectin Glycoprotein Ligand-1

“…Whereas the current study relies on gene overexpression, additional studies where ST6GalNAc2 is either knocked down in human cells or deleted in mice can strengthen the potential role of this enzyme. Indeed mice lacking ST6GalNAc2 have recently been created in a 129 parental background, and these animals display reduced body weight and B-cell proliferation defects (49). The leukocyte selectin-dependent adhesion function is yet unreported, although this is worth investigating.…”