Linked Life Data

11743578

Source:http://linkedlifedata.com/resource/pubmed/id/11743578

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-12-25
pubmed:databankReference
pubmed:abstractText
Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (GpnmbR150X) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to GpnmbR150X; otherwise, similar D2 mice that are not homozygous for GpnmbR150X do not develop IPD. ISA is caused by the recessive Tyrp1b mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-5
pubmed:dateRevised
2010-6-10
pubmed:meshHeading
pubmed-meshheading:11743578-Animals, pubmed-meshheading:11743578-Atrophy, pubmed-meshheading:11743578-Chromosome Mapping, pubmed-meshheading:11743578-Chromosomes, Artificial, Bacterial, pubmed-meshheading:11743578-Codon, Nonsense, pubmed-meshheading:11743578-Codon, Terminator, pubmed-meshheading:11743578-Crosses, Genetic, pubmed-meshheading:11743578-Epistasis, Genetic, pubmed-meshheading:11743578-Eye Proteins, pubmed-meshheading:11743578-Genetic Predisposition to Disease, pubmed-meshheading:11743578-Glaucoma, Open-Angle, pubmed-meshheading:11743578-Haplotypes, pubmed-meshheading:11743578-Humans, pubmed-meshheading:11743578-Iris, pubmed-meshheading:11743578-Melanosomes, pubmed-meshheading:11743578-Membrane Glycoproteins, pubmed-meshheading:11743578-Mice, pubmed-meshheading:11743578-Mice, Inbred C57BL, pubmed-meshheading:11743578-Mice, Inbred DBA, pubmed-meshheading:11743578-Molecular Sequence Data, pubmed-meshheading:11743578-Oxidoreductases, pubmed-meshheading:11743578-Pigments, Biological, pubmed-meshheading:11743578-Proteins, pubmed-meshheading:11743578-Recombination, Genetic, pubmed-meshheading:11743578-Specific Pathogen-Free Organisms
pubmed:year
2002
pubmed:articleTitle
Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice.
pubmed:affiliation
The Howard Hughes Medical Institute, Bar Harbor, Maine 04609, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.