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  • The EMBO Journal (2003) 22, 236 - 245
  • doi:10.1093/emboj/cdg019

Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney

Maarit Rossi1, Hiroyuki Morita2, Raija Sormunen3, Sari Airenne4, Marjut Kreivi1, Ling Wang2, Naomi Fukai5, Bjorn R. Olsen5, Karl Tryggvason2 and Raija Soininen1,2

  1. Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, FIN-90014 Oulu, Finland
  2. Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
  3. Biocenter Oulu, Department of Pathology, FIN-90014 Oulu, Finland
  4. Biocenter Oulu, Department of Biochemistry University of Oulu, FIN-90014 Oulu, Finland
  5. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA

Correspondence to:

Raija Soininen, E-mail: raija.soininen@oulu.fi

Received 18 July 2002; Accepted 14 November 2002; Revised 12 November 2002

Mice lacking exon 3 of perlecan (Hspg2) gene were generated by gene targeting. Exon deletion does not alter the expression or the reading frame but causes loss of attachment sites for three heparan sulfate (HS) side chains. Hspg2Delta3/Delta3 mice are viable and fertile but have small eyes. Apoptosis and leakage of cellular material through the lens capsule are observed in neonatal lenses, and lenses degenerate within 3 weeks of birth. Electron microscopy revealed altered structure of the lens capsule through which cells had formed extensions. No kidney malfunction, such as protein uria, was detected in Hspg2Delta3/Delta3 mutant mice, nor were ultrastructural changes observed in the glomerular basement membranes (BMs). To achieve further depletion in the HS content of the BMs, Hspg2Delta3/Delta3 mice were bred with collagen XVIII null mice. Lens defects were more severe in the newborn Col18a1-/- times Hspg2Delta3/Delta3 mice and degeneration proceeded faster than in Hspg2Delta3/Delta3 mice. The results suggest that in the lens capsule, HS chains have a structural function and are essential in the insulation of the lens from its environment and in regulation of incoming signals.

  • Keywords:

    • basement membranes,
    • collagen XVIII,
    • congenital cataract,
    • heparan sulfate,
    • perlecan