title: An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.
abstract: 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.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: D
authors.initials: D
authors.lastname: van de Pol
authors.forename: D
authors.initials: D
authors.lastname: Bächner
authors.forename: F
authors.initials: F
authors.lastname: Oerlemans
authors.forename: H
authors.initials: H
authors.lastname: Winkens
authors.forename: H
authors.initials: H
authors.lastname: Hameister
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
authors.forename: W
authors.initials: W
authors.lastname: Hendriks
authors.forename: H H
authors.initials: HH
authors.lastname: Ropers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001766:Blindness / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009928:Organ Specificity; D010786:Photoreceptor Cells / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012165:Retinal Ganglion Cells / Q000473:pathology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014822:Vitreous Body / Q000473:pathology
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; C489916:Ndph protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger