In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys

Am J Pathol. 2003 Jul;163(1):145-55. doi: 10.1016/S0002-9440(10)63638-3.


The nail-patella syndrome (NPS) is characterized by nail and bone abnormalities, associated with glomerular involvement in approximately 40% of patients. Typical glomerular changes consist of fibrillar material in the irregularly thickened glomerular basement membrane. NPS is inherited as an autosomal dominant trait and caused by heterozygous loss of function mutations in LMX1B, a member of the LIM homeodomain protein family. Mice with homozygous inactivation of the gene exhibit nail and skeletal defects, similar to those observed in patients, associated with glomerular abnormalities. Strong reduction in the glomerular expression of the alpha3 and alpha4 chains of type IV collagen, and of podocin and CD2AP, two podocyte proteins critical for glomerular function, has been observed in Lmx1b null mice. The expression of these proteins appeared to be regulated by Lmx1b. To determine whether these changes in podocyte gene expression are involved in the development of NPS nephropathy, using immunohistological techniques, we analyzed the podocyte phenotype and the renal distribution of type IV collagen chains in the kidneys of seven NPS patients with severe glomerular disease. We also examined the nature of the fibrillar material present within the glomerular extracellular matrix. The glomerular basement membrane fibrillar material was specifically labeled with anti-type III collagen antibodies, suggesting a possible regulation of type III collagen expression by LMX1B. The expression of the alpha3 and alpha4 chains of type IV collagen, and of podocin and CD2AP, was found to be normal in the seven patients. These findings indicate that heterozygous mutations of LMX1B do not appear to dramatically affect the expression of type IV collagen chains, podocin, or CD2AP in NPS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adolescent
  • Adult
  • Animals
  • Antibodies / metabolism
  • Child
  • Child, Preschool
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism*
  • Cytoskeletal Proteins
  • Female
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiology*
  • Kidney Glomerulus / ultrastructure
  • LIM-Homeodomain Proteins
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Nail-Patella Syndrome / genetics
  • Nail-Patella Syndrome / metabolism*
  • Nail-Patella Syndrome / pathology
  • Proteins / metabolism
  • Transcription Factors


  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • CD2-associated protein
  • Collagen Type IV
  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • LIM homeobox transcription factor 1 beta
  • LIM-Homeodomain Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Proteins
  • Transcription Factors
  • nephrin