Ra. Williamson et al., DYSTROGLYCAN IS ESSENTIAL FOR EARLY EMBRYONIC-DEVELOPMENT - DISRUPTION OF REICHERTS-MEMBRANE IN DAG1-NULL MICE, Human molecular genetics, 6(6), 1997, pp. 831-841
Dystroglycan is a central component of the dystrophin-glycoprotein com
plex (DGC), a protein assembly that plays a critical role in a variety
of muscular dystrophies. In order to better understand the function o
f dystroglycan in development and disease, we have generated a null al
lele of dystroglycan (Dag1(neo2)) in mice. Heterozygous Dag1(neo2) mic
e are viable and fertile. In contrast, homozygous Dag1(neo2) embryos e
xhibit gross developmental abnormalities beginning around 6.5 days of
gestation, Analysis of the mutant phenotype indicates that an early de
fect in the development of homozygous Dag1(neo2) embryos is a disrupti
on of Reichert's membrane, an extra-embryonic basement membrane. Consi
stent with the functional defects observed in Reichert's membrane, dys
troglycan protein is localized in apposition to this structure in norm
al egg cylinder stage embryos. We also show that the localization of t
wo critical structural elements of Reichert's membrane-laminin and col
lagen IV-are specifically disrupted in the homozygous Dag1(neo2) embry
os. Taken together, the data indicate that dystroglycan is required fo
r the development of Reichert's membrane. Furthermore, these results s
uggest that disruption of basement membrane organization might be a co
mmon feature of muscular dystrophies linked to the DGC.