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A Comprehensive Analysis of the Expression of Crystallins in Mouse Retina Jinghua Xi Washington University School of Medicine in St
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2003 A comprehensive analysis of the expression of crystallins in mouse retina Jinghua Xi Washington University School of Medicine in St. Louis Rafal Farjo University of Michigan - Ann Arbor Shigeo Yoshida University of Michigan - Ann Arbor Timothy S. Kern Case Western Reserve University Anand Swaroop University of Michigan - Ann Arbor See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Xi, Jinghua; Farjo, Rafal; Yoshida, Shigeo; Kern, Timothy S.; Swaroop, Anand; and Andley, Usha P., ,"A comprehensive analysis of the expression of crystallins in mouse retina." Molecular Vision.9,. 410-419. (2003). https://digitalcommons.wustl.edu/open_access_pubs/1801 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Jinghua Xi, Rafal Farjo, Shigeo Yoshida, Timothy S. Kern, Anand Swaroop, and Usha P. Andley This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/1801 Molecular Vision 2003; 9:410-9 <http://www.molvis.org/molvis/v9/a53> © 2003 Molecular Vision Received 28 May 2003 | Accepted 19 August 2003 | Published 28 August 2003 A comprehensive analysis of the expression of crystallins in mouse retina Jinghua Xi,1 Rafal Farjo,3 Shigeo Yoshida,3 Timothy S. Kern,5 Anand Swaroop,3,4 Usha P. Andley1,2 Departments of 1Ophthalmology and Visual Sciences and 2Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. -
Related Macular Degeneration and Cutis Laxa
UvA-DARE (Digital Academic Repository) Genetic studies of age-related macular degeneration Baas, D.C. Publication date 2012 Document Version Final published version Link to publication Citation for published version (APA): Baas, D. C. (2012). Genetic studies of age-related macular degeneration. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:05 Oct 2021 G������ S������ �� A��-������� M������ D����������� D����������� M������ G������ S������ �� A��-������� | 2012 D�������� C. B��� G������ S������ �� A��-������� M������ D����������� D�������� C. B��� cover.indd 1 31-10-12 08:36 Genetic Studies of Age-related Macular Degeneration Dominique C. Baas Chapter 0.indd 1 23-10-12 19:24 The research described in this thesis was conducted at the Netherlands Institute for Neuroscience (NIN), an institute of the Royal Netherlands Academy of Arts and Sciences, Department of Clinical and Molecular Ophthalmogenetics, Amsterdam, The Netherlands. -
Congenital Cataracts Due to a Novel 2‑Bp Deletion in CRYBA1/A3
1614 MOLECULAR MEDICINE REPORTS 10: 1614-1618, 2014 Congenital cataracts due to a novel 2‑bp deletion in CRYBA1/A3 JING ZHANG1, YANHUA ZHANG1, FANG FANG1, WEIHONG MU1, NING ZHANG2, TONGSHUN XU3 and QINYING CAO1 1Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital; 2Department of Cardiology, The Second Hospital of Hebei Medical University; 3Department of Surgery, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, Hebei, P.R. China Received September 22, 2013; Accepted April 11, 2014 DOI: 10.3892/mmr.2014.2324 Abstract. Congenital cataracts, which are a clinically and located in the eye lens. The major human crystallins comprise genetically heterogeneous group of eye disorders, lead to 90% of protein in the mature lens and contain two different visual impairment and are a significant cause of blindness superfamilies: the small heat‑shock proteins (α-crystallins) in childhood. A major proportion of the causative mutations and the βγ-crystallins. for congenital cataracts are found in crystallin genes. In the In this study a functional candidate approach was used present study, a novel deletion mutation (c.590-591delAG) in to investigate the known crystallin genes, including CRYAA, exon 6 of CRYBA1/A3 was identified in a large family with CRYAB, CRYBA1/A3, CRYBB1, CRYBB2, CRYGC, CRYGD autosomal dominant congenital cataracts. An increase in and CRYGS, in which a major proportion of the mutations local hydrophobicity was predicted around the mutation site; identified in a large family with congenital cataracts were however, further studies are required to determine the exact found. effect of the mutation on βA1/A3-crystallin structure and function. To the best of our knowledge, this is the first report Subjects and methods of an association between a frameshift mutation in exon 6 of CRYBA1/A3 and congenital cataracts. -
Congenital Eye Disorders Gene Panel
Congenital eye disorders gene panel Contact details Introduction Regional Genetics Service Ocular conditions are highly heterogeneous and show considerable phenotypic overlap. 1 in Levels 4-6, Barclay House 2,500 children in the UK are diagnosed as blind or severely visually impaired by the time they 37 Queen Square reach one year old. As many as half of these cases are likely to be inherited and remain undiagnosed due to the vast number of genes involved in these conditions. Many congenital London, WC1N 3BH eye disorders causing visual impairment or blindness at birth or progressive visual impairment T +44 (0) 20 7762 6888 also include syndromic conditions involving additional metabolic, developmental, physical or F +44 (0) 20 7813 8578 sensory abnormalities. Gene panels offer the enhanced probability of diagnosis as a very large number of genes can be interrogated. Samples required Ocular birth defects include all inheritance modalities. Autosomal dominant and recessive 5ml venous blood in plastic EDTA diseases as well as X-linked dominant and recessive diseases are seen. These conditions can bottles (>1ml from neonates) also be caused by de novo variants. Prenatal testing must be arranged Referrals in advance, through a Clinical Genetics department if possible. Patients presenting with a phenotype appropriate for the requested sub-panel Amniotic fluid or CV samples Referrals will be accepted from clinical geneticists and consultants in ophthalmology. should be sent to Cytogenetics for Prenatal testing dissecting and culturing, with instructions to forward the sample Prenatal diagnosis may be offered as appropriate where pathogenic variants have been to the Regional Molecular Genetics identified in accordance with expected inheritance pattern and where appropriate parental laboratory for analysis testing and counselling has been conducted. -
A Novel Γd-Crystallin Mutation Causes Mild Changes in Protein Properties but Leads to Congenital Coralliform Cataract
Molecular Vision 2009; 15:1521-1529 <http://www.molvis.org/molvis/v15/a162> © 2009 Molecular Vision Received 29 April 2009 | Accepted 3 August 2009 | Published 6 August 2009 A novel γD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract Li-Yun Zhang,1 Bo Gong,1 Jian-Ping Tong,2 Dorothy Shu-Ping Fan,1 Sylvia Wai-Yee Chiang,1 Dinghua Lou,2 Dennis Shun-Chiu Lam,1 Gary Hin-Fai Yam,1 Chi-Pui Pang1 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; 2Department of Ophthalmology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China Purpose: To identify the genetic lesions for congenital coralliform cataract. Methods: Two Chinese families with autosomal dominant coralliform cataract, 12 affected and 14 unaffected individuals, were recruited. Fifteen known genes associated with autosomal dominant congenital cataract were screened by two-point linkage analysis with gene based single nucleotide polymorphisms and microsatellite markers. Sequence variations were identified. Recombinant FLAG-tagged wild type or mutant γD-crystallin was expressed in human lens epithelial cells and COS-7 cells. Protein solubility and intracellular distribution were analyzed by western blotting and immunofluorescence, respectively. Results: A novel heterozygous change, c.43C>A (R15S) of γD-crystallin (CRYGD) co-segregated with coralliform cataract in one family and a known substitution, c.70C>A (P24T), in the other family. Unaffected family members and 103 unrelated control subjects did not carry these mutations. Similar to the wild type protein, R15S γD-crystallin was detergent soluble and was located in the cytoplasm. -
A Recurrent Mutation in CRYGD Is Associated with Autosomal Dominant Congenital Coralliform Cataract in Two Unrelated Chinese Families
Molecular Vision 2011; 17:1085-1089 <http://www.molvis.org/molvis/v17/a123> © 2011 Molecular Vision Received 29 March 2011 | Accepted 19 April 2011 | Published 28 April 2011 A recurrent mutation in CRYGD is associated with autosomal dominant congenital coralliform cataract in two unrelated Chinese families Guoxing Yang,1 Chunlei Xiong,2 Shanlan Li,2 Yuanyuan Wang,2 Jialiang Zhao1 1Department of Opthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; 2Department of Opthalmology, Hai Cheng Rehabilitation Hospital, Liaoning, China Purpose: Congenital cataract is a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the mutation responsible for autosomal dominant congenital coralliform cataracts in two Chinese families and to investigate the relationship between virulence genes and lens morphology. Methods: Patients received a physical examination, and blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the candidate genes: gammaC-crystallin (CRYGC), gammaD-crystallin (CRYGD), gammaS-crystallin (CRYGS), gap-junction protein, alpha 8 (GJA8), gap-junction protein, alpha 3 (GJA3), and alphaA-crystallin (CRYAA). Results: The affected individuals in two families had congenital coralliform cataracts. Mutational analysis of the CRYGD identified a C→A transversion at nucleotide position c.70 in exon 2, which resulted in a threonine substitution for proline at amino-acid residue 24 (P24T). This mutation was identified in all affected individuals but was not found in healthy relatives or 100 control chromosomes from the same ethnic background. Conclusions: Our results indicated that the P24T mutation of CRYGD was responsible for two Chinese pedigrees with congenital coralliform cataracts. -
Crystallin, Γ-Crystallin and GJA8 Gene in Congenital Cataract
Molecular Vision 2011; 17:693-707 <http://www.molvis.org/molvis/v17/a79> © 2011 Molecular Vision Received 10 October 2010 | Accepted 7 March 2011 | Published 11 March 2011 Mutation screening and genotype phenotype correlation of α- crystallin, γ-crystallin and GJA8 gene in congenital cataract Manoj Kumar,1 Tushar Agarwal,2 Sudarshan Khokhar,2 Manoj Kumar,3 Punit Kaur,3 Tara Sankar Roy,4 Rima Dada1 1Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India; 2Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India; 3Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India; 4Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India Purpose: To screen α-crystallin (CRYAB), γ-crystallin (CRYGC and CRYGD), and Connexin 50 (Cx-50 or GJA8) genes in congenital cataract patients and controls. Methods: Thirty clinically diagnosed congenital cataract cases below 3 years of age from northern India, presenting at Dr. R. P. Centre for Ophthalmic Sciences (AIIMS, New Delhi, India) were enrolled in this study. Genomic DNA was extracted from peripheral blood, all coding and exon/intron regions were amplified using PCR and direct sequencing was performed to detect any nucleotide variation. ProtScale and Discovery Studio programs were used for insilico and structural analysis of non-synonymous mutations. Results: DNA sequencing analysis of CRYAB, CRYGC, CRYGD, and GJA8 showed a total of six variations of which two were novel (CRYGC:p.R48H and GJA8:p.L281C) and four have been previously reported (CRYAB: rs11603779T>G, GJA8: p.L268L, CRYGD: p.R95R, and c.T564C). -
Zebrafish Model in Ophthalmology to Study Disease Mechanism And
pharmaceuticals Review Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery Yiwen Hong and Yan Luo * State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China; [email protected] * Correspondence: [email protected]; Tel.: +86-020-87335931 Abstract: Visual impairment and blindness are common and seriously affect people’s work and quality of life in the world. Therefore, the effective therapies for eye diseases are of high priority. Zebrafish (Danio rerio) is an alternative vertebrate model as a useful tool for the mechanism elucidation and drug discovery of various eye disorders, such as cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, photoreceptor degeneration, etc. The genetic and embryonic accessibility of zebrafish in combination with a behavioral assessment of visual function has made it a very popular model in ophthalmology. Zebrafish has also been widely used in ocular drug discovery, such as the screening of new anti-angiogenic compounds or neuroprotective drugs, and the oculotoxicity test. In this review, we summarized the applications of zebrafish as the models of eye disorders to study disease mechanism and investigate novel drug treatments. Keywords: zebrafish; eye; disease model; mechanism; drug candidate Citation: Hong, Y.; Luo, Y. Zebrafish Model in Ophthalmology to Study 1. Introduction Disease Mechanism and Drug Until 2020, an estimated 295 million people suffer from the moderate and severe visual Discovery. Pharmaceuticals 2021, 14, impairment worldwide, and among them, about 43.3 million people are even blind [1]. 716. https://doi.org/10.3390/ The leading global causes of blindness are cataract, followed by glaucoma, age-related ph14080716 macular degeneration (AMD), and diabetic retinopathy (DR) [2]. -
Rescue of Retinal Degeneration by Intravitreally Injected Adult Bone Marrow–Derived Lineage-Negative Hematopoietic Stem Cells
Rescue of retinal degeneration by intravitreally injected adult bone marrow–derived lineage-negative hematopoietic stem cells Atsushi Otani, … , John Heckenlively, Martin Friedlander J Clin Invest. 2004;114(6):765-774. https://doi.org/10.1172/JCI21686. Article Stem cells Inherited retinal degenerations afflict 1 in 3,500 individuals and are a heterogeneous group of diseases that result in profound vision loss, usually the result of retinal neuronal apoptosis. Atrophic changes in the retinal vasculature are also observed in many of these degenerations. While it is thought that this atrophy is secondary to diminished metabolic demand in the face of retinal degeneration, the precise relationship between the retinal neuronal and vascular degeneration is not clear. In this study we demonstrate that whenever a fraction of mouse or human adult bone marrow– derived stem cells (lineage-negative hematopoietic stem cells [Lin– HSCs]) containing endothelial precursors stabilizes and rescues retinal blood vessels that would ordinarily completely degenerate, a dramatic neurotrophic rescue effect is also observed. Retinal nuclear layers are preserved in 2 mouse models of retinal degeneration, rd1 and rd10, and detectable, albeit severely abnormal, electroretinogram recordings are observed in rescued mice at times when they are never observed in control-treated or untreated eyes. The normal mouse retina consists predominantly of rods, but the rescued cells after treatment with Lin– HSCs are nearly all cones. Microarray analysis of rescued retinas demonstrates -
Novel Mutation in the Γ-S Crystallin Gene Causing Autosomal Dominant Cataract
Molecular Vision 2009; 15:476-481 <http://www.molvis.org/molvis/v15/a48> © 2009 Molecular Vision Received 24 December 2008 | Accepted 27 February 2009 | Published 4 March 2009 Novel mutation in the γ-S crystallin gene causing autosomal dominant cataract Vanita Vanita,1 Jai Rup Singh,1 Daljit Singh,2 Raymonda Varon,3 Karl Sperling3 1Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, India; 2Dr. Daljit Singh Eye Hospital, Amritsar, India; 3Institute of Human Genetics, Charitè, University Medicine of Berlin, Berlin, Germany Purpose: To identify the underlying genetic defect in a north Indian family with seven members in three-generations affected with bilateral congenital cataract. Methods: Detailed family history and clinical data were recorded. Linkage analysis using fluorescently labeled microsatellite markers for the already known candidate gene loci was performed in combination with mutation screening by bidirectional sequencing. Results: Affected individuals had bilateral congenital cataract. Cataract was of opalescent type with the central nuclear region denser than the periphery. Linkage was excluded for the known cataract candidate gene loci at 1p34–36, 1q21–25 (gap junction protein, alpha 8 [GJA8]), 2q33–36 (crystallin, gamma A [CRYGA], crystallin, gamma B [CRYGB], crystallin, gamma C [CRYGC], crystallin, gamma D [CRYGD], crystallin, beta A2 [CRYBA2]), 3q21–22 (beaded filament structural protein 2, phakinin [BFSP2]), 12q12–14 (aquaporin 0 [AQP0]), 13q11–13 (gap junction protein, alpha 3 [GJA3]), 15q21– 22, 16q22–23 (v-maf musculoaponeurotic fibrosarcoma oncogene homolog [MAF], heat shock transcription factor 4 [HSF4]), 17q11–12 (crystallin, beta A1 [CRYBA1]), 17q24, 21q22.3 (crystallin, alpha A [CRYAA]), and 22q11.2 (crystallin, beta B1 [CRYBB1], crystallin, beta B2 [CRYBB2], crystallin, beta B3 [CRYBB3], crystallin, beta A4 [CRYBA4]). -
In Vivo and in Vitro Analysis of Dll1 and Pax6 Function in the Adult Mouse Pancreas
TECHNISCHE UNIVERSITÄT MÜNCHEN Lehrstuhl für Experimentelle Genetik In vivo and in vitro analysis of Dll1 and Pax6 function in the adult mouse pancreas Davide Cavanna Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. D. Langosch Prüfer der Dissertation: 1. Univ.-Prof. Dr. M. Hrabé de Angelis 2. Univ.-Prof. A. Schnieke, Ph.D. Die Dissertation wurde am 03.07.2013 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 10.12.2013 angenommen. I. Table of contents I. TABLE OF CONTENTS .................................................................................................. I II. FIGURES AND TABLES ................................................................................................ V III. ABBREVIATIONS ................................................................................................. VIII IV. PUBLICATIONS, TALKS, AND POSTERS ................................................................... XI V. ACKNOWLEDGMENTS .............................................................................................. XII VI. AFFIRMATION ..................................................................................................... XIV 1. SUMMARY/ZUSAMMENFASSUNG ............................................................................ -
The GJA8 Allele Encoding CX50I247M Is a Rare Polymorphism, Not a Cataract-Causing Mutation
Molecular Vision 2009; 15:1881-1885 <http://www.molvis.org/molvis/v15/a200> © 2009 Molecular Vision Received 7 July 2009 | Accepted 11 September 2009 | Published 14 September 2009 The GJA8 allele encoding CX50I247M is a rare polymorphism, not a cataract-causing mutation Jochen Graw,1 Werner Schmidt,2 Peter J. Minogue,3 Jessica Rodriguez,3 Jun-Jie Tong,4 Norman Klopp,5 Thomas Illig,5 Lisa Ebihara,4 Viviana M. Berthoud,3 Eric C. Beyer3 1Helmholtz Center Munich - German Research Center for Environmental Health, Institute of Developmental Genetics, D-85764 Neuherberg, Germany; 2Center of Ophthalmology, Universities of Gießen and Marburg, D-35385 Gießen, Germany; 3Department of Pediatrics, Section of Hematology/Oncology, University of Chicago, Chicago, IL; 4Department of Physiology and Biophysics, Rosalind Franklin School of Medicine and Science, North Chicago, IL; 5Helmholtz Center Munich - German Research Center for Environmental Health, Institute of Epidemiology, D-85764 Neuherberg, Germany Purpose: The aim of this study was the genetic, cellular, and physiological characterization of a connexin50 (CX50) variant identified in a child with congenital cataracts. Methods: Lens material from surgery was collected and used for cDNA production. Genomic DNA was prepared from blood obtained from the proband and her parents. PCR amplified DNA fragments were sequenced and characterized by restriction digestion. Connexin protein distribution was studied by immunofluorescence in transiently transfected HeLa cells. Formation of functional channels was assessed by two-microelectrode voltage-clamp in cRNA-injected Xenopus oocytes. Results: Ophthalmologic examination showed that the proband suffered from bilateral white, diffuse cataracts, but the parents were free of lens opacities. Direct sequencing of the PCR product produced from lens cDNA showed that the proband was heterozygous for a G>T transition at position 741 of the GJA8 gene, encoding the exchange of methionine for isoleucine at position 247 of CX50 (CX50I247M).