DOCSLIB.ORG

Mouse Models Neal S. Peachey Cole Eye Institute, Cleveland

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mouse Models Neal S. Peachey Cole Eye Institute, Cleveland Session 4-1 Impaired transmission from photoreceptors to bipolar cells: mouse models Neal S. Peachey Cole Eye Institute, ClevelandClinic Foundation, Cleveland, Ohio, USA Research Service,Cleveland VA Medical Center, Cleveland, Ohio, USA In response to light, photoreceptors normally decrease the rate of glutamate release at their terminal. This change is detected by two classes of bipolar cells, which are distinguished by whether they depolarize (DBCs) or hyperpolarize (HBCs) in response to light. The electroretinogram (ERG) can be used to monitor this process as the ERG a-wave reflects photoreceptor activity while the b-wave is generated by bipolar cell responses. As a consequence, a selective reduction in the ERG b-wave is usually indicative of a defect in transmission between photoreceptors and bipolar cells. This situation is encountered in naturally occurring and genetically engineered mice, the study of which shed light on the development and maintenance of the photoreceptor-to-bipolar cell synaptic process. For example, null mutations in the genes encoding mGluR6 or G• 0 eliminate the b-wave and confirm the role of these proteins in DBC signal transduction. A similar ERG pattern is seen in the nob (no b-wave) mouse, which is caused by a defect in nyx, encoding nyctalopin. Although the precise function of nyctalopin is unknown, the localization of nyctalopin transcripts to the outer nuclear layer indicates that this protein may play a critical role in the DBC response. Despite the lack of DBC function, ribbon synapses form normally in nob mice. Presynaptically, glutamate release is controlled by L-type calcium channels located on the photoreceptor terminal. The b-wave is selectively reduced in CNS• 2-null mice, lacking the •2 subunit of the L-type calcium channel in the central nervous system. In addition, the normal distribution of the pore-forming • 1F subunit is markedly disturbed, indicating that the • 2 subunit is required to guide the formation of a functional channel. Such channels are likely to be required for ribbon synapse formation, as ribbon structures are rarely encountered in CNS• 2-null mice. As the nob and CNS• 2-null mice involve genes that underlie two forms of congenital stationary night blindness, study of these animal models will expand our understanding of these rare human disorders. Keywords: mouse, electroretinogram, retina 21 Session 4-2 Selective dysfunction of On and/or Off-bipolar cell in human diseases Yozo Miyake, Mineo Kondo, Makoto Nakamura and Hiroko Terasaki Departmentof Ophthalmology,Nagoya UniversitySchool of Medicine,Nagoya, Japan In human, cone visual signals in the retina are processed through dual pathways, one involving ON-center bipolar cells (ON-pathway) and the other through OFF-center bipolar cells (the OFF-pathway), while rod visual signal is processed only through ON-pathway. Little is known about how the patients can see when ON and/or OFF-pathway are defective selectively. By comparing the monkey's ERG (electroretinogram) blocked ON- or OFF-pathway using glutamate neurotransmitter analogs, we have detected new clinical entities in human where ON- and/or OFF-pathway are blocked in both rod and cone visual pathways. We hypothesized that complete type congenital stationary night blindness (CSNB 1) can be a model disease having a complete dysfunction of only ON-pathway, while incomplete type (CSNB 2) has an incomplete dysfunction of both ON and OFF-pathway in both rod and cone visual systems. The gene mutation was detected in nyctalopin in CSNB 1, and in L-type calcium channel ƒ¿l subunit in CSNB 2. We analyzed 90 patients (49 patients with CSNB 1, 41 patients with CSNB 2) in terms of scotopic vision (dark adaptation) and photopic vision (visual acuity, contrast sensitivity and color vision). The scotopic vision was found to be impaired completely and incompletely in CSNB 1 and CSNB 2, respectively. The photopic visions are better preserved than we expected even when the full-field photopic ERG showed complete defect of ON-visual pathway. Judging from the findings of focal macular cone ERG, we found that the macula of these patients is selectively spared from the generalized defect of entire retina. Keywords: bipolar cell dysfunction, ERG, psychophysical function 22.
Load more

Recommended publications
  • Recessive Mutations of the Gene TRPM1 Abrogate on Bipolar Cell Function and Cause Complete Congenital Stationary Night Blindness in Humans
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REPORT Recessive Mutations of the Gene TRPM1 Abrogate ON Bipolar Cell Function and Cause Complete Congenital Stationary Night Blindness in Humans Zheng Li,1 Panagiotis I. Sergouniotis,1 Michel Michaelides,1,2 Donna S. Mackay,1 Genevieve A. Wright,2 Sophie Devery,2 Anthony T. Moore,1,2 Graham E. Holder,1,2 Anthony G. Robson,1,2 and Andrew R. Webster1,2,* Complete congenital stationary night blindness (cCSNB) is associated with loss of function of rod and cone ON bipolar cells in the mammalian retina. In humans, mutations in NYX and GRM6 have been shown to cause the condition. Through the analysis of a consan- guineous family and screening of nine additional pedigrees, we have identified three families with recessive mutations in the gene TRPM1 encoding transient receptor potential cation channel, subfamily M, member 1, also known as melastatin. A number of other variants of unknown significance were found. All patients had myopia, reduced central vision, nystagmus, and electroretinographic evidence of ON bipolar cell dysfunction. None had abnormalities of skin pigmentation, although other skin conditions were reported. RNA derived from human retina and skin was analyzed and alternate 50 exons were determined. The most 50 exon is likely to harbor an initiation codon, and the protein sequence is highly conserved across vertebrate species. These findings suggest an important role of this specific cation channel for the normal function of ON bipolar cells in the human retina. Congenital stationary night blindness (CSNB) is a group of of the gene encoding transient receptor potential cation genetically determined, nondegenerative disorders of the channel, subfamily M, member 1 (TRPM1 [MIM *603576]) retina associated with lifelong deficient vision in the dark has been discovered in the skin and retina of horses homo- and often nystagmus and myopia.
    [Show full text]
  • Two Novel NYX Gene Mutations in the Chinese Families with X-Linked
    www.nature.com/scientificreports OPEN Two Novel NYX Gene Mutations in the Chinese Families with X-linked Congenital Stationary Night Received: 24 November 2014 Accepted: 30 March 2015 Blindness Published: 03 August 2015 Shuzhen Dai1,2,*, Ming Ying2,3,*, Kai Wang2,3, Liming Wang2,3, Ruifang Han2,3, Peng Hao2,3 & Ningdong Li2,3 Mutations in NYX and CACNA1F gene are responsible for the X-linked congenital stationary night blindness (CSNB). In this study, we described the clinical characters of the two Chinese families with X-linked CSNB and detected two novel mutations of c. 371_377delGCTACCT and c.214A>C in the NYX gene by direct sequencing. These two mutations would expand the mutation spectrum of NYX. Our study would be helpful for further studying molecular pathogenesis of CSNB. Congenital stationary night blindness (CSNB) is a group of clinically and genetically heterogeneous reti- nal disorders characterized by night blindness, decreased visual acuity, and a reduced or absent b-wave in the electroretinogram (ERG)1. Other clinical features of CSNB may include variable degrees of myopia, a nearly normal fundus appearance, nystagmus and strabismus. Two subgroups of CSNB can be classi- fied by ERG into the “complete form” (or type 1 CSNB), and “incomplete form” (or type 2 CSNB)2. The complete form is characterized by absence of rod b-wave and oscillatory potentials due to complete loss of the rod pathway function, whereas the incomplete form shows a reduced rod b-wave, cone a-wave, and 30-Hz flicker ERG response caused by impaired rod and cone pathway function3. CSNB may be inherited as an autosomal dominant, autosomal recessive and X-linked inheritance mode.
    [Show full text]
  • A Role for Nyctalopin, a Small Leucine-Rich Repeat Protein, in Localizing the TRP Melastatin 1 Channel to Retinal Depolarizing Bipolar Cell Dendrites
    10060 • The Journal of Neuroscience, July 6, 2011 • 31(27):10060–10066 Cellular/Molecular A Role for Nyctalopin, a Small Leucine-Rich Repeat Protein, in Localizing the TRP Melastatin 1 Channel to Retinal Depolarizing Bipolar Cell Dendrites Jillian N. Pearring,1* Pasano Bojang Jr,1* Yin Shen,3 Chieko Koike,4,5 Takahisa Furukawa,4 Scott Nawy,3 and Ronald G. Gregg1,2 Departments of 1Biochemistry and Molecular Biology and 2Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky 40202, 3Departments of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York 10461, 4Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan, and 5PRESTO, Japanese Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan Expressionofchannelstospecificneuronalsitescancriticallyimpacttheirfunctionandregulation.Currently,themolecularmechanisms underlying this targeting and intracellular trafficking of transient receptor potential (TRP) channels remain poorly understood, and identifying proteins involved in these processes will provide insight into underlying mechanisms. Vision is dependent on the normal function of retinal depolarizing bipolar cells (DBCs), which couple a metabotropic glutamate receptor 6 to the TRP melastatin 1 (TRPM1) channel to transmit signals from photoreceptors. We report that the extracellular membrane-attached protein nyctalopin is required for the normal expression of TRPM1 on the dendrites of DBCs in mus musculus. Biochemical and genetic data indicate that nyctalopin and TRPM1 interact directly, suggesting that nyctalopin is acting as an accessory TRP channel subunit critical for proper channel localization to the synapse. Introduction largely intracellular role, possibly regulating melanin produc- Being in the right place at the right time is fundamental for sig- tion (Oancea et al., 2009; Patel and Docampo, 2009).
    [Show full text]
  • Thirty Distinct CACNA1F Mutations in 33 Families with Incomplete Type of XLCSNB and Cacna1f Expression Profiling in Mouse Retina
    European Journal of Human Genetics (2002) 10, 449 – 456 ª 2002 Nature Publishing Group All rights reserved 1018 – 4813/02 $25.00 www.nature.com/ejhg ARTICLE Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina Krisztina Wutz1, Christian Sauer2, Eberhart Zrenner3, Birgit Lorenz4, Tiina Alitalo5, Martina Broghammer6, Martin Hergersberg7, Albert de La Chapelle5, Bernhard HF Weber2, Bernd Wissinger6, Alfons Meindl*,1 and Carsten M Pusch6,8 1Abteilung Medizinische Genetik der LMU, Mu¨nchen, Germany; 2Institut fu¨r Humangenetik, Biozentrum, Wu¨rzburg, Germany; 3Abteilung fu¨r Pathophysiologie des Sehens und Neuro-Ophthalmologie, Universita¨tsaugenklinik, Tu¨bingen, Germany; 4Abteilung fu¨r Kinderophthalmologie, Strabismologie und Ophthalmogenetik, Klinikum der Universita¨t, Regensburg, Germany; 5Helsinki University Hospital, Helsinki, Finland; 6Molekulargenetisches Labor der Universita¨tsaugenklinik, Tu¨bingen, Germany; 7Medizinische Genetik der Universita¨t, Zu¨rich, Switzerland; 8Institut fu¨r Anthropologie und Humangenetik, Tu¨bingen, Germany X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel a1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as A˚ land Island eye disease (A˚ IED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population.
    [Show full text]
  • Resisting Drugs New Light on Night Blindness
    HIGHLIGHTS HUMAN GENETICS New light on night blindness Courtesy of Robert Gwadz. X-linked congenital stationary night rich repeats (LRRs), an amino-terminal MALARIA blindness (CSNB) is a non-progressive signal peptide, a possible carboxy-termi- retinal disorder that is characterized by nal cleavage site, and a glycosylation site, impaired night vision, reduced visual acu- among other motifs. Both teams propose Resisting drugs ity, and frequently, although not always, that nyctalopin is cleaved at the carboxyl by nystagmus (uncontrollable eye move- terminus and is GPI-anchored at the Chloroquine is a safe and cheap antimalarial drug — ment) and myopia. There are two forms extracellular cell membrane as a glycosy- and it used to be effective. But the malaria parasite, of the condition, called complete and lated proteoglycan. It is likely that the Plasmodium falciparum, has fought back by incomplete X-linked CSNB, which are LRRs confer on nyctalopin the ability to developing drug resistance. The rising prevalence of distinguishable by measuring the electro- interact with other proteins. LRRs can chloroquine resistance is increasing still further the physiological responses of the retina to mediate diverse biological functions, health threat posed by malaria. There is an urgent light. The gene for the incomplete form including cell adhesion and migration — need to understand the basis of chloroquine was identified in 1998, and now, two years in Drosophila melanogaster, for example, resistance (CQR), and genetic studies have just on, Nature Genetics reports the cloning of two LRR proteins, chaoptin and capri- opened the door. the gene for complete CSNB. cious, are cell adhesion molecules that Ten years ago, it was shown that CQR segregates as Two research teams tracked down this are crucial for fly neuronal development.
    [Show full text]
  • Human Recombinant Protein – TP316019
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP316019 NYX (NM_022567) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human nyctalopin (NYX) Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 49.5 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_072089 Locus ID: 60506 UniProt ID: Q9GZU5 RefSeq Size: 2713 Cytogenetics: Xp11.4 RefSeq ORF: 1443 Synonyms: CLRP; CSNB1; CSNB1A; CSNB4; NBM1 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 NYX (NM_022567) Human Recombinant Protein – TP316019 Summary: The product of this gene belongs to the small leucine-rich proteoglycan (SLRP) family of proteins. Defects in this gene are the cause of congenital stationary night blindness type 1 (CSNB1), also called X-linked congenital stationary night blindness (XLCSNB). CSNB1 is a rare inherited retinal disorder characterized by impaired scotopic vision, myopia, hyperopia, nystagmus and reduced visual acuity.
    [Show full text]
  • Gene Expression in the Mouse Eye: an Online Resource for Genetics Using 103 Strains of Mice
    Molecular Vision 2009; 15:1730-1763 <http://www.molvis.org/molvis/v15/a185> © 2009 Molecular Vision Received 3 September 2008 | Accepted 25 August 2009 | Published 31 August 2009 Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice Eldon E. Geisert,1 Lu Lu,2 Natalie E. Freeman-Anderson,1 Justin P. Templeton,1 Mohamed Nassr,1 Xusheng Wang,2 Weikuan Gu,3 Yan Jiao,3 Robert W. Williams2 (First two authors contributed equally to this work) 1Department of Ophthalmology and Center for Vision Research, Memphis, TN; 2Department of Anatomy and Neurobiology and Center for Integrative and Translational Genomics, Memphis, TN; 3Department of Orthopedics, University of Tennessee Health Science Center, Memphis, TN Purpose: Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology. Methods: mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts. Results: We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences.
    [Show full text]
  • Agricultural University of Athens
    ΓΕΩΠΟΝΙΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΣΧΟΛΗ ΕΠΙΣΤΗΜΩΝ ΤΩΝ ΖΩΩΝ ΤΜΗΜΑ ΕΠΙΣΤΗΜΗΣ ΖΩΙΚΗΣ ΠΑΡΑΓΩΓΗΣ ΕΡΓΑΣΤΗΡΙΟ ΓΕΝΙΚΗΣ ΚΑΙ ΕΙΔΙΚΗΣ ΖΩΟΤΕΧΝΙΑΣ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ ΑΘΗΝΑ 2020 ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Genome-wide association analysis and gene network analysis for (re)production traits in commercial broilers ΕΙΡΗΝΗ Κ. ΤΑΡΣΑΝΗ ΕΠΙΒΛΕΠΩΝ ΚΑΘΗΓΗΤΗΣ: ΑΝΤΩΝΙΟΣ ΚΟΜΙΝΑΚΗΣ Τριμελής Επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Επταμελής εξεταστική επιτροπή: Aντώνιος Κομινάκης (Αν. Καθ. ΓΠΑ) Ανδρέας Κράνης (Eρευν. B, Παν. Εδιμβούργου) Αριάδνη Χάγερ (Επ. Καθ. ΓΠΑ) Πηνελόπη Μπεμπέλη (Καθ. ΓΠΑ) Δημήτριος Βλαχάκης (Επ. Καθ. ΓΠΑ) Ευάγγελος Ζωίδης (Επ.Καθ. ΓΠΑ) Γεώργιος Θεοδώρου (Επ.Καθ. ΓΠΑ) 2 Εντοπισμός γονιδιωματικών περιοχών και δικτύων γονιδίων που επηρεάζουν παραγωγικές και αναπαραγωγικές ιδιότητες σε πληθυσμούς κρεοπαραγωγικών ορνιθίων Περίληψη Σκοπός της παρούσας διδακτορικής διατριβής ήταν ο εντοπισμός γενετικών δεικτών και υποψηφίων γονιδίων που εμπλέκονται στο γενετικό έλεγχο δύο τυπικών πολυγονιδιακών ιδιοτήτων σε κρεοπαραγωγικά ορνίθια. Μία ιδιότητα σχετίζεται με την ανάπτυξη (σωματικό βάρος στις 35 ημέρες, ΣΒ) και η άλλη με την αναπαραγωγική
    [Show full text]
  • Congenital Disorder of Glycosylation Due to Phosphomannomutase Deficiency
    CLINICAL SCIENCES Retinal On-Pathway Deficit in Congenital Disorder of Glycosylation Due to Phosphomannomutase Deficiency Dorothy A. Thompson, PhD; Ruth J. Lyons, PhD; Alki Liasis, PhD; Isabelle Russell-Eggitt, MD; Herbert Ja¨gle, MD, FEBO; Stephanie Gru¨newald, MD Objective: To describe novel electroretinographic (ERG) attenuated to the fifth percentile, whereas scotopic findings associated with congenital disorder of glyco- a-wave amplitudes were at the 50th to 75th percentile, giv- sylation due to phosphomannomutase deficiency (PMM2- ing a reduced a:b ratio. The scotopic a-wave waveform was CDG) (previously known as congenital disorder of gly- well defined to bright flash luminance. The number of sco- cosylation type 1a). topic oscillatory potentials was preserved, although am- plitudes were smaller than average. Scotopic 15-Hz flicker Methods: Two male siblings with genetically con- ERGs were evident to a range of flash luminances and firmed PMM2-CDG underwent full-field ERG to a range showed an expected phase cancellation between −1.5 and of scotopic and photopic flash luminances that ex- −1.0 log scotopic td (troland) • s, but phase increased only tended the International Society for Clinical Electro- for the fast rod pathway. physiology of Vision standard protocol and included sco- topic 15-Hz flicker and photopic prolonged on-off Conclusions: We find, for the first time to our knowl- stimulation. edge, an association of PMM2-CDG with a selective on- pathway dysfunction in the retina. This ERG phenotype Results: Photopic prolonged ERGs were profoundly elec- localizes the site of retinal dysfunction to the on-bipolar tronegative with absent b-waves but preserved oscilla- synapse with photoreceptors.
    [Show full text]
  • In Vivo Development of Retinal ON-Bipolar Cell Axonal Terminals Visualized in Nyx::MYFP Transgenic Zebrafish
    Visual Neuroscience ~2006!, 23, 833–843. Printed in the USA. Copyright © 2006 Cambridge University Press 0952-5238006 $16.00 DOI: 10.10170S0952523806230219 In vivo development of retinal ON-bipolar cell axonal terminals visualized in nyx::MYFP transgenic zebrafish ERIC H. SCHROETER,1 RACHEL O.L. WONG,1* and RONALD G. GREGG2* 1Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 2Department of Biochemistry and Molecular Biology, and Center for Genetics and Molecular Medicine, University of Louisville, Louisville, Kentucky (Received February 13, 2006; Accepted May 12, 2006! Abstract Axonal differentiation of retinal bipolar cells has largely been studied by comparing the morphology of these interneurons in fixed tissue at different ages. To better understand how bipolar axonal terminals develop in vivo,we imaged fluorescently labeled cells in the zebrafish retina using time-lapse confocal and two photon microscopy. Using the upstream regulatory sequences from the nyx gene that encodes nyctalopin, we constructed a transgenic fish in which a subset of retinal bipolar cells express membrane targeted yellow fluorescent protein ~MYFP!. Axonal terminals of these YFP-labeled bipolar cells laminated primarily in the inner half of the inner plexiform layer, suggesting that they are likely to be ON-bipolar cells. Transient expression of MYFP in isolated bipolar cells indicates that two or more subsets of bipolar cells, with one or two terminal boutons, are labeled. Live imaging of YFP-expressing bipolar cells in the nyx::MYFP transgenic fish at different ages showed that initially, filopodial-like structures extend and retract from their primary axonal process throughout the inner plexiform layer ~IPL!.
    [Show full text]
  • (Nyctalopin on Chromosome X), the Gene Mutated in Congenital Stationary Night Blindness, Encodes a Cell Surface Protein
    NYX (Nyctalopin on Chromosome X), the Gene Mutated in Congenital Stationary Night Blindness, Encodes a Cell Surface Protein Christina Zeitz,1,2,3,4 Harry Scherthan,2,4 Susanne Freier,2 Silke Feil,1,2 Vanessa Suckow,2 Susann Schweiger,2 and Wolfgang Berger1,2 PURPOSE. The complete type of X-linked congenital stationary and are functionally conserved. (Invest Ophthalmol Vis Sci. night blindness (CSNB1) in human and mouse is caused by 2003;44:4184–4191) DOI:10.1167/iovs.03-0251 mutations in the NYX gene. The human NYX protein has been predicted to contain an N-terminal endoplasmic reticulum (ER) -linked congenital stationary night blindness (XLCSNB) is a signaling sequence and a C-terminal glycosylphosphatidylinosi- Xnonprogressive retinal disorder characterized by impaired tol (GPI) anchor. In the current study, these computer predic- night vision and other ocular symptoms such as myopia, hy- tions were verified experimentally by expression of domain- peropia, nystagmus, and reduced visual acuity.1 According to specific cDNA constructs in COS-7 and HeLa cells. Moreover, the clinical phenotype, XLCSNB can be divided into two types: computer-based analysis of the orthologue mouse amino acid complete (CSNB1) and incomplete (CSNB2). These two sub- sequence did not reveal a GPI anchor, which may result in a types can be distinguished on the basis of electroretinogram different protein localization compared with human NYX. (ERG) and by genetic means.2,3 CSNB2 is associated with a Therefore, the cellular localization for the mouse Nyx protein reduced rod b-wave and substantially reduced cone response was also examined. and is due to mutations in CACNA1F, an X chromosomal gene METHODS.
    [Show full text]
  • V13a36-Zhang Pgmkr
    Molecular Vision 2007; 13:330-6 <http://www.molvis.org/molvis/v13/a36/> ©2007 Molecular Vision Received 2 May 2006 | Accepted 27 February 2007 | Published 1 March 2007 Mutations in NYX of individuals with high myopia, but without night blindness Qingjiong Zhang,1 Xueshan Xiao,1 Shiqiang Li,1 Xiaoyun Jia,1 Zhikuan Yang,1 Shizhou Huang,1 Rafael C. Caruso,2 Tianqin Guan,1 Yuri Sergeev,2 Xiangming Guo,1 J. Fielding Hejtmancik2 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; 2Oph- thalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD Purpose: High myopia is a common genetic variant that severely affects vision. Genes responsible for myopia without linked additional functional defects have not been identified. Mutations in the nyctalopin gene (NYX) located at Xp11.4 are responsible for a complete form of congenital stationary night blindness (CSNB1). High myopia is usually observed in patients with CSNB1. This study was designed to test the possibility that mutations in the NYX gene might cause high myopia without congenital stationary night blindness (CSNB). Methods: The genomic sequence of NYX in 52 male probands with high myopia but without CSNB was analyzed through direct DNA sequencing. Variations in the NYX were verified by analyzing available family members and 232 controls. Results: Two unrelated male individuals with high myopia but without night blindness were found to have novel Cys48Trp and Arg191Gln mutations in NYX. The mutations were found to be located in distinct regions, different from the locations of mutations known to cause congenital stationary night blindness with myopia (CSNB1).
    [Show full text]