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

Michael G Anderson; K Saidas Nair; Leslie A Amonoo; Adrienne Mehalow; Colleen M Trantow; Sharmila Masli; Simon WM John

doi:10.1186/1471-2156-9-30

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

Journal article

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

Michael G Anderson, K Saidas Nair, Leslie A Amonoo, Adrienne Mehalow, Colleen M Trantow, Sharmila Masli and Simon WM John

BMC genetics, Vol.9(1), pp.30-30

04/10/2008

DOI: 10.1186/1471-2156-9-30

PMCID: PMC2373794

PMID: 18402690

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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.

Details

Title: Subtitle: GpnmbR150X allele must be present in bone marrow derived cells to mediate DBA/2J glaucoma
Creators: Michael G Anderson - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa USA
K Saidas Nair - The Jackson Laboratory, Bar Harbor, Maine, USA
Leslie A Amonoo - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa USA
Adrienne Mehalow - The Jackson Laboratory, Bar Harbor, Maine, USA
Colleen M Trantow - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa USA
Sharmila Masli - Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
Simon WM John - The Jackson Laboratory, Bar Harbor, Maine, USA
Resource Type: Journal article
Publication Details: BMC genetics, Vol.9(1), pp.30-30
DOI: 10.1186/1471-2156-9-30
PMID: 18402690
PMCID: PMC2373794
NLM abbreviation: BMC Genet
ISSN: 1471-2156
eISSN: 1471-2156
Publisher: BioMed Central
Language: English
Date published: 04/10/2008
Academic Unit: Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
Record Identifier: 9984025694802771

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