A 9.5 day old mouse embryo with blue color showing where a gene important for glycosylation is expressed. Image credit: Lukacs et al. (CC BY 4.0)
Many of the proteins that cells produce have sugar molecules attached to them. These additions, called glycosylations, often help to deliver proteins to the parts of the cell where they are needed. In some genetic disorders, individuals have gene mutations that prevent glycosylation from occurring properly. This can lead to a variety of symptoms including seizures, cleft palates and heart defects. It was not clear how changes in glycosylation cause these symptoms.
A GPI anchor is a specific glycosylation that helps to attach many different proteins to the outer membrane of cells. Lukacs et al. created mouse models with genetic mutations that prevent GPI anchors from forming correctly, and studied the effects these had in mouse embryos. This revealed that a loss of GPI anchors early in embryonic development causes the cells that produce the face to die, as they are very sensitive to an early loss of glycosylation. Because too few face cells survive, embryos develop cleft palate, and other reductions in facial tissues. However, giving the embryos supplements of folinic acid in the womb reduced these effects.
In the future, further experiments using the genetically altered mice generated by Lukacs et al. could explore how glycosylation affects the development of other tissues and organs, like the heart and liver. This could ultimately help researchers to predict the effects of certain genetic conditions and to develop new treatments for them.
