Phenotype changes of Fut8 knockout mouse: core fucosylation is crucial for the function of growth factor receptor(s)

Methods Enzymol. 2006;417:11-22. doi: 10.1016/S0076-6879(06)17002-0.

Abstract

Alpha1,6-fucosyltransferase (Fut8) catalyzes the transfer of a fucose residue to N-linked oligosaccharides on glycoproteins by means of an alpha1,6-linkage to form core fucosylation in mammals. In mice, disruption of Fut8 induces severe growth retardation, early death during postnatal development, and emphysema-like changes in the lung. A marked dysregulation of TGF-beta1 receptor activation and signaling in Fut8-null mice lung results in overexpression of matrix metalloproteinases (MMPs), such as MMP12 and MMP13, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, which contributes to the destructive emphysema-like phenotype observed in Fut8-null mice. Furthermore, therapeutic administration of exogenous TGF-beta1 rescued the null mice from the emphysema-like phenotype. On the other hand, absence of Fut8 on EGF or PDGF receptor results in down-regulation of the receptor-mediated signaling, which is a plausible factor that may be responsible for the growth retardation. Reintroduction of the Fut8 gene to Fut8-null cells potentially rescued these receptor-mediated signaling impaired in null cells. Collectively, these results suggest that core fucosylation is crucial for growth factor receptors such as TGF-beta1 and EGF receptor-mediated biological functions.

Publication types

  • Review

MeSH terms

  • Animals
  • Fucose / metabolism*
  • Fucosyltransferases / deficiency
  • Fucosyltransferases / genetics*
  • Mice
  • Mice, Knockout
  • Phenotype
  • Receptors, Growth Factor / metabolism
  • Receptors, Growth Factor / physiology*

Substances

  • Receptors, Growth Factor
  • Fucose
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase