The γ3 chain of laminin is widely but differentially expressed in murine basement membranes: expression and functional studies

Matrix Biol. 2012 Mar;31(2):120-34. doi: 10.1016/j.matbio.2011.12.002. Epub 2011 Dec 24.

Abstract

Laminins are heterotrimeric extracellular glycoproteins found in, but not confined to, basement membranes (BMs). They are important components in formation of the molecular networks of BMs as well as in cell polarity, cell differentiation and tissue morphogenesis. Each laminin is composed by an α, a β and a γ chain. Previous studies have shown that the γ3 chain is partnered with either the β1 chain (in placenta) or β2 chain (in the CNS) (Libby et al., 2000). Several studies, including our own, suggested that the γ3 chain is expressed in both apical and basal compartments (Koch et al., 1999; Gersdorff et al., 2005; Yan and Cheng, 2006). This study investigates the expression pattern of the γ3 chain in mouse. We developed three new γ3-reactive antibodies, and we show that the γ3 chain is present in BMs. The distribution pattern is considerably more restricted than that of the γ1 chain and within any tissue there is differential deposition into BM compartments. This is particularly true in the retina and brain, where γ3 is uniquely expressed in a subset of the vascular basement membranes and the pial surface. We used conventional genetic ablation techniques to remove the γ3 chain in mice; unlike other laminin null mice (α5, β2, γ1 nulls), these mice live a normal lifespan and have only minor abnormalities, the most striking of which are ectopic granule cells in the cerebellum and an apparent increase in capillary branching in the outer retina. These data support the suggestion that the γ3 chain is deposited in BMs and contributes some unique properties to their function, particularly in the nervous system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Antibodies / metabolism
  • Basement Membrane / cytology
  • Basement Membrane / metabolism*
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Cloning, Molecular
  • Gene Expression Regulation*
  • Heterozygote
  • Immunohistochemistry
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Laminin / genetics
  • Laminin / metabolism*
  • Longevity
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neurons / cytology
  • Neurons / metabolism
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retina / metabolism
  • Retina / pathology
  • Retinal Neovascularization / metabolism
  • Retinal Neovascularization / pathology

Substances

  • Antibodies
  • Integrin beta1
  • Lamc3 protein, mouse
  • Laminin
  • Recombinant Proteins