An Animal Model for Norrie Disease (ND): Gene Targeting of the Mouse Nd Gene

In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with it...

Full description

Saved in:
Bibliographic Details
Published in:Human molecular genetics 1996-01, Vol.5 (1), p.51-59
Main Authors: Berger, Wolfgang, van de Pol, Dorien, Bächner, Dietmar, Oerlemans, Frank, Winkens, Huub, Hameister, Horst, Wieringa, Bé, Hendriks, Wiljan, Ropers, Hans-Hilger
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biological and medical sciences
Blindness - genetics
Cloning, Molecular
Exons - genetics
Eye Proteins - genetics
Female
Gene Targeting - methods
Humans
Male
Malformations of the eye
Medical sciences
Mice
Mice, Knockout - genetics
Molecular Sequence Data
Nerve Tissue Proteins - genetics
Ophthalmology
Organ Specificity
Photoreceptor Cells - pathology
Retinal Ganglion Cells - pathology
RNA, Messenger - analysis
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Vitreous Body - pathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/5.1.51