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.