PMID- 10192392
OWN - NLM
STAT- MEDLINE
DCOM- 19990426
LR  - 20100610
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 4
DP  - 1999 Apr
TI  - Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.
PG  - 405-9
AB  - Glaucomas are a major cause of blindness. Visual loss typically involves retinal 
      ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation 
      of intraocular pressure (IOP). Some human glaucomas are associated with anterior 
      segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy 
      with associated synechiae. The primary causes of these abnormalities are unknown,
      and their aetiology is poorly understood. We recently characterized a mouse
      strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes
      including pigment dispersion and iris atrophy. Using crosses between mouse
      strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal
      regions that contribute to the anterior segment changes and glaucoma. Progeny
      homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an
      iris pigment dispersion phenotype similar to human PDS. ipd resides on a region
      of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q
      that is associated with human PDS. Progeny homozygous for the D2 allele of a
      different locus on chromosome 4 (called isa) develop an iris stromal atrophy
      phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via 
      a mechanism involving pigment production. Progeny homozygous for the D2 alleles
      of both ipd and isa develop an earlier onset and more severe disease involving
      pigment dispersion and iris stromal atrophy.
FAU - Chang, B
AU  - Chang B
AD  - The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
FAU - Smith, R S
AU  - Smith RS
FAU - Hawes, N L
AU  - Hawes NL
FAU - Anderson, M G
AU  - Anderson MG
FAU - Zabaleta, A
AU  - Zabaleta A
FAU - Savinova, O
AU  - Savinova O
FAU - Roderick, T H
AU  - Roderick TH
FAU - Heckenlively, J R
AU  - Heckenlively JR
FAU - Davisson, M T
AU  - Davisson MT
FAU - John, S W
AU  - John SW
LA  - eng
GR  - CA34196/CA/NCI NIH HHS/United States
GR  - EY07758/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.14.18.- (TYRP1 protein, human)
RN  - EC 1.14.18.- (Tyrp1 protein, mouse)
RN  - EC 1.14.18.- (tyrosinase-related protein-1)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Atrophy
MH  - Chromosome Mapping
MH  - Crosses, Genetic
MH  - Glaucoma/*genetics
MH  - Homozygote
MH  - Iris/*pathology
MH  - Iris Diseases/*genetics/pathology
MH  - *Membrane Glycoproteins
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA/*genetics
MH  - Mice, Inbred Strains
MH  - Microsatellite Repeats
MH  - *Oxidoreductases
MH  - Pigment Epithelium of Eye/pathology
MH  - Proteins/genetics
MH  - Species Specificity
EDAT- 1999/04/07 02:01
MHDA- 2001/03/23 10:01
CRDT- 1999/04/07 02:01
PHST- 1999/04/07 02:01 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/07 02:01 [entrez]
AID - 10.1038/7741 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Apr;21(4):405-9. doi: 10.1038/7741.