title: Iris transillumination defect and its gene modulators do not correlate with intraocular pressure in the BXD family of mice.
abstract: OBJECTIVE
  Intraocular pressure (IOP) is currently the only treatable phenotype associated with primary open angle glaucoma (POAG). Our group has developed the BXD murine panel for identifying genetic modulators of the various endophenotypes of glaucoma, including pigment dispersion, IOP, and retinal ganglion cell (RGC) death. The BXD family consists of the inbred progeny of crosses between the C57BL/6J (B6) strain and the glaucoma-prone DBA/2J (D2) strain that has mutations in Tyrp1 and Gpnmb. The role of these genes in the iris transillumination defect (TID) has been well documented; however, their possible roles in modulating IOP during glaucoma onset and progression are yet not well understood.
  
  
  METHODS
  We used the IOP data sets and the Eye M430v2 (Sep08) RMA Database available on GeneNetwork to determine whether mutations in Tyrp1 and Gpnmb or TIDs have a direct role in the elevation of IOP in the BXD family. We also determined whether TIDs and IOP are coregulated.
  
  
  RESULTS
  As expected, Tyrp1 and Gpnmb expression levels showed a high degree of correlation with TIDs. However, there was no correlation between the expression of these genes and IOP. Moreover, unlike TIDs, IOP did not map to either the Tyrp1 or Gpnmb locus. Although the Tyrp1 and Gpnmb mutations in BXD strains are a prerequisite for the development of TID, they are not required for or associated with elevated IOP.
  
  
  CONCLUSIONS
  Genetic modulators of IOP thus may be independently identified using the full array of BXD mice without concern for the presence of TIDs or mutations in Typr1 and/or Gpnmb.
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN; Department of Ophthalmology, Nantong Eye Institute, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN; Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D053263:Gene Regulatory Networks; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D007429:Intraocular Pressure / Q000235:genetics*; D007499:Iris Diseases / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010088:Oxidoreductases / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014065:Tonometry, Ocular; D014172:Transillumination
chemical_list: D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse