Advanced

Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration

Friedman, James S. ; Chang, Bo ; Kannabiran, Chitra ; Chakarova, Christina ; Singh, Hardeep P. ; Jalali, Subhadra ; Hawes, Norman L. ; Branham, Kari ; Othman, Mohammad and Filippova, Elena , et al. (2006) In American Journal of Human Genetics 79(6). p.1059-1070
Abstract
The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C -> T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies.... (More)
The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C -> T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Human Genetics
volume
79
issue
6
pages
1059 - 1070
publisher
Cell Press
external identifiers
  • wos:000242131600007
  • scopus:33845205060
ISSN
0002-9297
language
English
LU publication?
yes
id
35a322ca-d3f7-48ad-9c55-38fe55018a12 (old id 376677)
alternative location
http://www.journals.uchicago.edu/AJHG/journal/issues/v79n6/44120/brief/44120.abstract.html
date added to LUP
2016-04-01 12:34:25
date last changed
2019-12-04 02:39:30
@article{35a322ca-d3f7-48ad-9c55-38fe55018a12,
  abstract     = {The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C -> T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing.},
  author       = {Friedman, James S. and Chang, Bo and Kannabiran, Chitra and Chakarova, Christina and Singh, Hardeep P. and Jalali, Subhadra and Hawes, Norman L. and Branham, Kari and Othman, Mohammad and Filippova, Elena and Thompson, Debra A. and Webster, Andrew R. and Andréasson, Sten and Jacobson, Samuel G. and Bhattacharya, Shomi S. and Heckenlively, John R. and Swaroop, Anand},
  issn         = {0002-9297},
  language     = {eng},
  number       = {6},
  pages        = {1059--1070},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration},
  url          = {http://www.journals.uchicago.edu/AJHG/journal/issues/v79n6/44120/brief/44120.abstract.html},
  volume       = {79},
  year         = {2006},
}