Genetic modulation of the iris transillumination defect: a systems genetics analysis using the expanded family of BXD glaucoma strains

Pigment Cell Melanoma Res. 2013 Jul;26(4):487-98. doi: 10.1111/pcmr.12106. Epub 2013 May 13.


We investigated the contributions of Tyrp1 and Gpnmb to the iris transillumination defect (TID) in five age cohorts of BXD mice. Using systems genetics, we also evaluated the role of other known pigmentation genes (PGs). Mapping studies indicate that Tyrp1 contributes to the phenotype at all ages, yet the TID maps to Gpnmb only in the oldest cohort. Composite interval mapping reveals secondary loci viz. Oca2, Myo5a, Prkcz, and Zbtb20 that modulate the phenotype in the age groups up to 10-13 months. The contributions of Tyrp1 and Gpnmb were highly significant in all age cohorts. Moreover, in young mice, all six gene candidates had substantial interactions in our model. Our model accounted for 71-88% of the explained variance of the TID phenotype across the age bins. These results demonstrate that along with Tyrp1 and Gpnmb, Oca2, Myo5a, Prkcz, and Zbtb20 modulate the TID in an age-dependent manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism, Oculocutaneous / genetics
  • Algorithms
  • Animals
  • Crosses, Genetic
  • Disease Models, Animal
  • Disease Progression
  • Eye Diseases / genetics
  • Eye Proteins / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Variation
  • Genome
  • Glaucoma / genetics*
  • Iris / pathology*
  • Linear Models
  • Male
  • Membrane Glycoproteins / genetics*
  • Mice
  • Oxidoreductases / genetics*
  • Phenotype
  • Pigmentation / genetics
  • Quantitative Trait Loci
  • Transillumination


  • Eye Proteins
  • Gpnmb protein, mouse
  • Membrane Glycoproteins
  • Oxidoreductases
  • Tyrp1 protein, mouse

Supplementary concepts

  • Oculocutaneous albinism type 2