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First published online 21 April 2004
doi: 10.1242/dev.01112
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1 Renal Division, Washington University School of Medicine, St Louis, MO 63110,
USA
2 Department of Cell Biology and Physiology, Washington University School of
Medicine, St Louis, MO 63110, USA
3 Department of Cell Biology, University of Virginia, Charlottesville, VA 22908,
USA
* Author for correspondence (e-mail: minerj{at}wustl.edu)
Accepted 29 January 2004
Laminins are components of all basement membranes and have well
demonstrated roles in diverse developmental processes, from the
peri-implantation period onwards. Laminin 1 (
1ß1
1) is a
major laminin found at early stages of embryogenesis in both embryonic and
extraembryonic basement membranes. The laminin 1 chain has been shown
by targeted mutation to be required for endodermal differentiation and
formation of basement membranes; Lamc1-/- embryos die
within a day of implantation. We report the generation of mice lacking laminin
1 and laminin ß1, the remaining two laminin 1 chains. Mutagenic
insertions in both Lama1 and Lamb1 were obtained in a
secretory gene trap screen. Lamb1-/- embryos are similar
to Lamc1-/- embryos in that they lack basement membranes
and do not survive beyond embryonic day (E) 5.5. However, in
Lama1-/- embryos, the embryonic basement membrane forms,
the embryonic ectoderm cavitates and the parietal endoderm differentiates,
apparently because laminin 10 (5ß11) partially compensates
for the absent laminin 1. However, such compensation did not occur for
Reichert's membrane, which was absent, and the embryos died by E7.
Overexpression of laminin 5 from a transgene improved the phenotype of
Lama1-/- embryos to the point that they initiated
gastrulation, but this overexpression did not rescue Reichert's membrane, and
trophoblast cells did not form blood sinuses. These data suggest that both the
molecular composition and the integrity of basement membranes are crucial for
early developmental events.
Key words: Laminin, Basement membrane, Embryogenesis, Mouse
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