GpnmbR150X allele must be present in bone marrow derived cells to mediate DBA/2J glaucoma.

Abstract

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.

• Authors: Michael G Anderson, K Saidas Nair, Leslie A Amonoo, Adrienne Mehalow, Colleen M Trantow, Sharmila Masli, Simon W M John
• Journal: BMC genetics (BMC Genet) Vol. 9 Pg. 30 (Apr 10 2008) ISSN: 1471-2156 [Electronic] England
• PMID: 18402690 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Eye Proteins
• Gpnmb protein, mouse
• Interleukin-18
• Membrane Glycoproteins

Topics

• Alleles
• Animals
• Antigen-Presenting Cells (immunology)
• Aqueous Humor (immunology)
• Bone Marrow Cells (immunology, physiology)
• Disease Susceptibility
• Eye Proteins (genetics)
• Genotype
• Glaucoma (genetics, immunology, physiopathology)
• Interleukin-18 (immunology)
• Intraocular Pressure (genetics)
• Membrane Glycoproteins (genetics)
• Mice
• Mice, Congenic
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Mutation