COL4A6 is dispensable for autosomal recessive Alport syndrome

Sci Rep. 2016 Jul 5;6:29450. doi: 10.1038/srep29450.


Alport syndrome is caused by mutations in the genes encoding α3, α4, or α5 (IV) chains. Unlike X-linked Alport mice, α5 and α6 (IV) chains are detected in the glomerular basement membrane of autosomal recessive Alport mice, however, the significance of this finding remains to be investigated. We therefore generated mice lacking both α3 and α6 (IV) chains and compared their renal function and survival with Col4a3 knockout mice of 129 × 1/Sv background. No significant difference was observed in the renal function or survival of the two groups, or when the mice were backcrossed once to C57BL/6 background. However, the survival of backcrossed double knockout mice was significantly longer than that of the mice of 129 × 1/Sv background, which suggests that other modifier genes were involved in this phenomenon. In further studies we identified two Alport patients who had a homozygous mutation in intron 46 of COL4A4. The α5 and α6 (IV) chains were focally detected in the glomerular basement membrane of these patients. These findings indicate that although α5 and α6 (IV) chains are induced in the glomerular basement membrane in autosomal recessive Alport syndrome, their induction does not seem to play a major compensatory role.

MeSH terms

  • Adolescent
  • Animals
  • Collagen Type IV / genetics*
  • Collagen Type IV / metabolism*
  • Crosses, Genetic
  • Female
  • Genes, Recessive*
  • Glomerular Basement Membrane / metabolism
  • Homozygote
  • Humans
  • Introns
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Nephritis, Hereditary / genetics*
  • Peptide Fragments / metabolism


  • COL4A1 protein, human
  • COL4A2 protein, human
  • COL4A6 protein, human
  • Col4a1 protein, mouse
  • Col4a2 protein, mouse
  • Collagen Type IV
  • Peptide Fragments