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J. Cell Biol.,
Volume 144, Number 1, January 11, 1999 151-160
* Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool L69 3GE, United Kingdom; The LAMC1 gene coding for the laminin Institute
for Biochemistry, University of Cologne, D-50931 Cologne, Germany; and § Department of Neurochemistry,
Max-Planck-Institute of Psychiatry, D-82152 Martinsried, Germany
1
subunit was targeted by homologous recombination in
mouse embryonic stem cells. Mice heterozygous for the
mutation had a normal phenotype and were fertile,
whereas homozygous mutant embryos did not survive
beyond day 5.5 post coitum. These embryos lacked
basement membranes and although the blastocysts had
expanded, primitive endoderm cells remained in the inner cell mass, and the parietal yolk sac did not develop.
Cultured embryonic stem cells appeared normal after targeting both LAMC1 genes, but the embryoid bodies
derived from them also lacked basement membranes,
having disorganized extracellular deposits of the basement membrane proteins collagen IV and perlecan, and
the cells failed to differentiate into stable myotubes. Secretion of the linking protein nidogen and a truncated
laminin 
1 subunit did occur, but these were not deposited in the extracellular matrix. These results show that
the laminin 1 subunit is necessary for laminin assembly and that laminin is in turn essential for the organization of other basement membrane components in vivo
and in vitro. Surprisingly, basement membranes are not
necessary for the formation of the first epithelium to
develop during embryogenesis, but first become required for extra embryonic endoderm differentiation.
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