Additional file 2.

Gpnmb^R150X mutation does not directly elevate IOP. Mean IOP ± SEM is presented. For ease of comparison, some of the data are duplicated from Figure 3. It is clear that the Gpnmb^R150X mutation contributes to the iris disease of DBA/2J mice and is a critical component of the glaucoma. Manipulations that prevent severe iris disease in DBA/2J mice prevent both anterior chamber enlargement (a marker of IOP elevation) and glaucoma development [20,22]. Thus, the iris disease is an essential component of the glaucoma. To determine if the Gpnmb^R150X mutation also influences IOP independently of the iris disease, we have assessed IOP in aged DBA/2J mice that have the Gpnmb mutation in all tissues but that do not develop the severe iris disease. These mice were homozygous for the wild-type C57BL/6J allele of Tyrp1 (Tyrp1^B6, that was backcrossed into DBA/2J for more than 10 generations) [34] and the mutant DBA/2J allele of Gpnmb (Gpnmb^D2 = Gpnmb^R150X). Since mutant DBA/2J alleles of both Tyrp1 and Gpnmb are necessary to develop severe iris disease, the Tyrp1^B6Gpnmb^D2 mice did not do so. Importantly and despite the presence of the Gpnmb mutation in the iris and bone marrow, the Tyrp1^B6 Gpnmb^D2 mice did not develop elevated IOP. Thus, the Gpnmb^R150X mutation does not induce high IOP directly but does so by inducing the iris disease.

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Anderson et al. BMC Genetics 2008 9:30   doi:10.1186/1471-2156-9-30