当前位置： SCI文献检索 > INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE期刊下所有文献 > Mpdz null allele in an avian model of retinal degeneration and mutations in human leber congenital amaurosis and retinitis pigmentosa.

Mpdz null allele in an avian model of retinal degeneration and mutations in human leber congenital amaurosis and retinitis pigmentosa.

Abstract：

PURPOSE:To identify the defective gene in the sex-linked, recessively inherited retinal dysplasia and degeneration (rdd) chicken and to search for the human equivalent disease. METHODS:Microsatellites from chicken chromosome Z were genotyped in 77 progeny of a carrier male (rdd/+) and an affected female (rdd/W), and candidate genes were sequenced. Retinal cross-sections from rdd and wild-type birds were analyzed by immunohistology. The human orthologous gene was screened in a panel of archival DNAs from 276 patients with retinitis pigmentosa (RP) or Leber congenital amaurosis (LCA) using melting curve analysis and DNA sequencing. RESULTS:The rdd locus was refined to an approximately 3-Mb region on chromosome Z. Sequence analysis identified a C→T change in the mpdz gene that created a premature stop codon (c.1372C→T, p.R458X), which segregated with the disease phenotype. As expected, the full-length mpdz protein was absent in rdd retinas, but in wild-type birds, it localized to the retinal outer limiting membrane, where it may have a role in the interactions between photoreceptors and Müller glia cells. The screen to identify the human equivalent disease found 10 heterozygous variants in the orthologous gene in patients with RP (three missense and two null alleles) and LCA (four missense and one null allele). CONCLUSIONS:These findings reveal that MPDZ is essential for normal development of the retina and may have a role in maintaining photoreceptor integrity. The identification of human mutations suggests that MPDZ plays a role in human retinal disease, but the precise nature of this role remains to be determined.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Ali M,Hocking PM,McKibbin M,Finnegan S,Shires M,Poulter JA,Prescott K,Booth A,Raashid Y,Jafri H,Ruddle JB,Mackey DA,Jacobson SG,Toomes C,Lester DH,Burt DW,Curry WJ,Inglehearn CF

doi

10.1167/iovs.11-7872

subject

Has Abstract

pub_date

2011-09-27 00:00:00

pages

7432-40

issue

eissn

0146-0404

issn

1552-5783

pii

iovs.11-7872

journal_volume

pub_type

杂志文章

在线工具

Mpdz null allele in an avian model of retinal degeneration and mutations in human leber congenital amaurosis and retinitis pigmentosa.