Disease relevance of Ndph

• Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse [1].
• Here we report that female mice homozygous for the Norrie disease pseudoglioma homolog (Ndph) knockout allele exhibit almost complete infertility, while heterozygous females and hemizygous males are fertile [2].
• PURPOSE: Mutations in the NDP gene give rise to a variety of eye diseases, including classic Norrie disease (ND), X-linked exudative vitreoretinopathy (EVRX), retinal telangiectasis (Coats disease), and advanced retinopathy of prematurity (ROP) [3].
• RESULTS: ACAID was readily induced in RCS rats and ND mice irrespective of amount of retinal degeneration or aging [4].
• RESULTS: Quantitative evaluation revealed an increase in the number of blood vessels in the interface of the ganglion cell layer and the nerve fiber layer and a decrease in the inner and outer plexiform layers in ND mice older than 9 days compared with control mice [5].

Psychiatry related information on Ndph

• Norrie disease (ND) is a severe form of congenital blindness accompanied by mental retardation and/or deafness in at least one third of the patients [6].

High impact information on Ndph

• 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 [7].
• 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 [7].
• Cellular retention studies showed that the receptor-bound radioiodinated linear alpha-MSH analog NDP was released from the cells into the medium very quickly, whereas significant amounts of cell-associated radioactivity remained in the cells for Ac-Lys((125)I-3- or 4-iodobenzoate (IBA))-ReCCMSH(Arg(11)) and Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) [8].
• PURPOSE: To investigate the nature and origin of the vitreous membranes in mice with knock-out of the Norrie gene product (ND mice) [9].
• The ND gene product neither influences endostatin expression nor the presence of macrophages [9].

Biological context of Ndph

• In the current study, gene expression was determined in a mouse model of ND, to unravel disease-associated mechanisms at the molecular level [3].
• Analysis of transcription initiation sites suggests the presence of multiple start sites associated with expression of the mouse NDP gene [10].
• Here, we identified and characterized rat Ndp, cow Ndp, chicken ndp and zebrafish ndp genes by using bioinformatics [11].
• Genetic linkage studies and physical mapping strategies have assigned the ND locus to the proximal short arm of the human X chromosome [6].
• Numerous point mutations in this gene have been identified in three distinct clinical entities: (1) ND, (2) familial and sporadic exudative vitreoretinopathy, and (3) retinopathy of prematurity [6].

Anatomical context of Ndph

• Although a recently identified, high-affinity FZD4 ligand Norrin (Norrie disease pseudoglioma homolog) is expressed in the ovary, adult Ndph-/- mice contain functional corpora lutea and do not phenocopy Fzd4-/- mice [12].
• Obviously, the absence of the Ndp gene product is not compatible with long-term survival of photoreceptor cells in the mouse [3].
• Using RT-PCR analyses we also demonstrate, for the first time, the expression of Ndph in mouse uteri and deciduae as well as the expression of NDP in human placenta [2].
• Some other DNase(s) may be present in the periplasm and responsible for a residual DNase activity, which was about one-fourth of that of the parent strain, detected in the ND mutant [13].
• NDP does not appear to correspond to any of the hitherto characterized neutrophil proteins and the only activity so far detected is a reaction of the protein with rat plasma (but not serum) [14].

Associations of Ndph with chemical compounds

• 19F NMR of 2-deoxy-2-fluoro-D-glucose for tumor diagnosis in mice. An NDP-bound hexose analog as a new NMR target for imaging [15].
• Available evidence suggests that NDP-kinase may be responsible for the activation of the guanine nucleotide-binding proteins (G1, G2 and p21 proteins) through phosphate transfer by the enzyme [16].

Analytical, diagnostic and therapeutic context of Ndph

• Histological examinations and RNA in situ hybridization analyses revealed defects in vascular development and decidualization in pregnant Ndph-/- females from embryonic day 7 (E7) onwards, resulting in embryonic loss [2].
• 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 [7].
• METHODS: Posterior eye segments of ND mice of different age groups were investigated by light and electron microscopy (EM) and scanning EM of vascular corrosion cast preparations [5].
• By PCR analysis, we found that expression of the NDP gene was not confined to the eye or to the brain [17].
• Molecular cloning and functional expression of the second mouse nm23/NDP kinase gene, nm23-M2 [18].

References