Angiogenesis

, Volume 16, Issue 3, pp 639–646

The albino mutation of tyrosinase alters ocular angiogenic responsiveness

  • Michael S. Rogers
  • Irit Adini
  • Aaron F. McBride
  • Amy E. Birsner
  • Robert J. D’Amato
Original Paper

DOI: 10.1007/s10456-013-9342-0

Cite this article as:
Rogers, M.S., Adini, I., McBride, A.F. et al. Angiogenesis (2013) 16: 639. doi:10.1007/s10456-013-9342-0

Abstract

We have observed substantial differences in angiogenic responsiveness in mice and have mapped the genetic loci responsible for these differences. We have found that the albino mutation is one of the loci responsible for such differences. Using B6.A consomic strains, we determined that chromosome 7 bears a locus that inhibits VEGF-induced corneal neovascularization. F2 crosses between B6.A<Chromosome 7> consomic mice and C57BL/6J parents along with AXB and BXA recombinant inbred strains demonstrated highest linkage near the tyrosinase gene. This region was named AngVq4. Congenic animals confirmed this locus, but could not demonstrate that the classical tyrosinase albino (c) mutation was causative because of the existence of additional linked loci in the congenic region. However, in 1970, a second tyrosinase albino mutation (c-2J) arose in the C57BL/6J background at Jackson Labs. Testing this strain (C57BL/6J<c-2J>) demonstrated that the albino mutation is sufficient to completely explain the alteration in angiogenic response that we observed in congenic animals. Thus, we conclude that the classical tyrosinase mutation is responsible for AngVq4. In contrast to the cornea, where pigmented animals exhibit increased angiogenic responsiveness, iris neovascularization was inhibited in pigmented animals. These results may partially explain increased aggressiveness in amelanotic melanoma, as well as ethnic differences in diabetic retinopathy and macular degeneration.

Keywords

QTL mappingPigmentAlbinoConsomic mouseCorneaIrisDOPADHI5,6-Dihydroxyindole

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Michael S. Rogers
    • 1
  • Irit Adini
    • 1
  • Aaron F. McBride
    • 1
  • Amy E. Birsner
    • 1
  • Robert J. D’Amato
    • 1
    • 2
  1. 1.Vascular Biology ProgramChildren’s Hospital Boston, Harvard Medical SchoolBostonUSA
  2. 2.Department of OphthalmologyHarvard Medical SchoolBostonUSA