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Molecular and Cellular Biology, February 2002, p. 1194-1202, Vol. 22, No. 4
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.4.1194-1202.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Deletion of the Laminin {alpha}4 Chain Leads to Impaired Microvessel Maturation

Jill Thyboll,1 Jarkko Kortesmaa,1,{dagger} Renhai Cao,2 Raija Soininen,1,{ddagger} Ling Wang,1,§ Antti Iivanainen,1,|| Lydia Sorokin,3 Mårten Risling,4,# Yihai Cao,2 and Karl Tryggvason1*

Division of Matrix Biology, Department of Medical Biochemistry and Biophysics,1 Microbiology and Tumor Biology Center,2 Department of Neuroscience, Karolinska Institutet, S-17 177 Stockholm, Sweden,4 Interdisciplinary Center for Clinical Research, Nikolaus Fiebiger Center, 91045 Erlangen, Germany3

Received 31 August 2001/ Returned for modification 26 October 2001/ Accepted 19 November 2001

The laminin {alpha}4 chain, a component of laminin-8 and -9, is expressed in basement membranes, such as those beneath endothelia, the perineurium of peripheral nerves, and around developing muscle fibers. Laminin {alpha}4-null mice presented with hemorrhages during the embryonic and neonatal period and had extensive bleeding and deterioration of microvessel growth in experimental angiogenesis, as well as mild locomotion defects. Histological examination of newborn mice revealed delayed deposition of type IV collagen and nidogen into capillary basement membranes, and electron microscopy showed discontinuities in the lamina densa. The results demonstrate a central role for the laminin {alpha}4 chain in microvessel growth and, in the absence of other laminin {alpha} chains, in the composition of endothelial basement membranes.

* Corresponding author. Mailing address: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17 177 Stockholm, Sweden. Phone: 46-8-728 7720. Fax: 46-8-316 165. E-mail: Karl.Tryggvason{at}mbb.ki.se.

{dagger} Present address: BioStratum AB, SE-171 77 Stockholm, Sweden.

{ddagger} Present address: Department of Medical Biochemistry, University of Oulu, FIN-90014 Finland.

§ Present address: The Burnham Institute, La Jolla, CA 92037.

|| Present address: Faculty of Veterinary Medicine, University of Helsinki, FIN-00014 Finland.

# Present address: The Swedish Defense Research Agency, S-172 24 Sundbyberg, Sweden.

Molecular and Cellular Biology, February 2002, p. 1194-1202, Vol. 22, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.4.1194-1202.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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