PMID- 10412977
OWN - NLM
STAT- MEDLINE
DCOM- 19990809
LR  - 20220408
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 98
IP  - 1
DP  - 1999 Jul 9
TI  - Insights into the function of Rim protein in photoreceptors and etiology of 
      Stargardt's disease from the phenotype in abcr knockout mice.
PG  - 13-23
AB  - Rim protein (RmP) is an ABC transporter of unknown function in rod outer segment 
      discs. The human gene for RmP (ABCR) is affected in several recessive retinal 
      degenerations. Here, we characterize the ocular phenotype in abcr knockout mice. 
      Mice lacking RmP show delayed dark adaptation, increased all-trans-retinaldehyde 
      (all-trans-RAL) following light exposure, elevated phosphatidylethanolamine (PE) 
      in outer segments, accumulation of the protonated Schiff base complex of 
      all-trans-RAL and PE (N-retinylidene-PE), and striking deposition of a major 
      lipofuscin fluorophore (A2-E) in retinal pigment epithelium (RPE). These data 
      suggest that RmP functions as an outwardly directed flippase for 
      N-retinylidene-PE. Delayed dark adaptation is likely due to accumulation in discs 
      of the noncovalent complex between opsin and all-trans-RAL. Finally, 
      ABCR-mediated retinal degeneration may result from "poisoning" of the RPE due to 
      A2-E accumulation, with secondary photoreceptor degeneration due to loss of the 
      RPE support role.
FAU - Weng, J
AU  - Weng J
AD  - Center for Basic Neuroscience and Department of Psychiatry, University of Texas 
      Southwestern Medical Center, Dallas 75235, USA.
FAU - Mata, N L
AU  - Mata NL
FAU - Azarian, S M
AU  - Azarian SM
FAU - Tzekov, R T
AU  - Tzekov RT
FAU - Birch, D G
AU  - Birch DG
FAU - Travis, G H
AU  - Travis GH
LA  - eng
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  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (ABCA4 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abca4 protein, mouse)
RN  - 0 (Phospholipids)
RN  - 9009-81-8 (Rhodopsin)
RN  - RR725D715M (Retinaldehyde)
SB  - IM
MH  - ATP-Binding Cassette Transporters/genetics/*physiology
MH  - Adaptation, Ocular
MH  - Animals
MH  - Darkness
MH  - Electroretinography
MH  - Genomic Library
MH  - Humans
MH  - Macular Degeneration/*genetics/physiopathology
MH  - Metabolic Clearance Rate
MH  - Mice
MH  - Mice, Knockout
MH  - Phenotype
MH  - Phospholipids/metabolism
MH  - Retina/physiology/physiopathology
MH  - Retinaldehyde/pharmacokinetics
MH  - Rhodopsin/metabolism
MH  - Rod Cell Outer Segment/chemistry/*physiopathology
EDAT- 1999/07/21 00:00
MHDA- 1999/07/21 00:01
CRDT- 1999/07/21 00:00
PHST- 1999/07/21 00:00 [pubmed]
PHST- 1999/07/21 00:01 [medline]
PHST- 1999/07/21 00:00 [entrez]
AID - S0092-8674(00)80602-9 [pii]
AID - 10.1016/S0092-8674(00)80602-9 [doi]
PST - ppublish
SO  - Cell. 1999 Jul 9;98(1):13-23. doi: 10.1016/S0092-8674(00)80602-9.