Syndecan-4 (Ryudocan) is a transmembrane protein with heparan
In situ hybridization and immunohistochemical staining demonstrated
that the expression of syndecan-4 in the microvasculature was restricted
to the placental labyrinth and the kidneys of adult mice. We have generated
syndecan-4 deficient [Synd4(-/-)] mice to investigate its biological functions.
The area of degeneration of the fetal vessels in the placental labyrinth
at 17.5 gestational days was more diffuse and larger in the placentas
of Synd4(-/-) embryos than wild-type [Synd4(+/+)] controls. Calcium deposition
at the degenerated vessels was also more extensive and severer in the
placentas of Synd4(-/-) embryos. When lipopolysaccharide or k-carrageenan
was injected intraperitoneally into pregnant Synd4(+/-) mice mated with
Synd4(+/-) males, intrauterine growth of Synd4(-/-) embryos was affected
more severely than that of Synd4(+/+) controls. Thus, syndecan-4 deficiency
impaired the fetal vessels in the placenta, especially under procoagulant
stress, likely due to a deficit in the anticoagulation mechanism.
Among a large number of core proteins of heparan sulfate proteoglycans,
it is the first report demonstrating that a defect of a single core protein
caused an increased blood coagulation in a specific site.