Author(s): Anderson MG, Nair KS, Amonoo LA, Mehalow A, Trantow CM, Masli S, John SW. GpnmbR150X allele must be present in bone marrow derived cells to mediate DBA/2J glaucoma. BMC Genet. 2008 Apr 10;9:30. doi: 10.1186/1471-2156-9-30. PMID 18402690
Journal: Bmc Genetics, Volume 9, Apr 2008
BACKGROUND The Gpnmb gene encodes a transmembrane protein whose function(s) remain largely unknown. Here, we assess if a mutant allele of Gpnmb confers susceptibility to glaucoma by altering immune functions. DBA/2J mice have a mutant Gpnmb gene and they develop a form of glaucoma preceded by a pigment dispersing iris disease and abnormalities of the immunosuppressive ocular microenvironment.
RESULTS We find that the Gpnmb genotype of bone-marrow derived cell lineages significantly influences the iris disease and the elevation of intraocular pressure. GPNMB localizes to multiple cell types, including pigment producing cells, bone marrow derived F4/80 positive antigen-presenting cells (APCs) of the iris and dendritic cells. We show that APCs of DBA/2J mice fail to induce antigen induced immune deviation (a form of tolerance) when treated with TGFbeta2. This demonstrates that some of the immune abnormalities previously identified in DBA/2J mice result from intrinsic defects in APCs. However, the tested APC defects are not dependent on a mutant Gpnmb gene. Finally, we show that the Gpnmb mediated iris disease does not require elevated IL18 or mature B or T lymphocytes.
CONCLUSION These results establish a role for Gpnmb in bone marrow derived lineages. They suggest that affects of Gpnmb on innate immunity influence susceptibility to glaucoma in DBA/2J mice.