Application of functional genomic technologies in a mouse model of retinal degeneration.

Generation of tissue-specific, normalized and subtracted cDNA libraries has the potential to characterize the expression of rare transcriptional units not represented on Affymetrix GeneChips. Initial sequence analysis of our murine cDNA clone collections showed that as much as 86, 45, and 30% of clones are not represented on the Affymetrix Mu11k, MG-U74, and MG-430 chip sets, respectively. A detailed study that compared EST sequences of a subtracted library generated from mouse retina to those of MG-430 consensus sequences was undertaken, using UniGene build 124 as the common reference. A set of 1111 nonredundant transcript regions, not represented on the commercial array, was identified. These clusters were used as the primary filter for analyzing a data set produced by assaying samples from the Pde6b(rd1) mouse model of retinal degeneration on a 12,325-feature retinal cDNA microarray. QRT-PCR validated eight unique transcripts identified by microarray. Seven of the transcripts showed retina-specific expression. Full-length cloning strategies were applied to two of the ESTs. The genes discovered by this approach are the full-length mouse homologue of guanylate cyclase 2F (GUCY2F) and a carboxy-truncated splice variant of retinal S-antigen (SAG), known as regulators of the visual phototransduction G-protein-coupled receptor-mediated signaling pathway. These sequences have been assigned GenBank Accession Nos. and , respectively.

[1]  Z. Tang,et al.  Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study , 2004, BMC Genomics.

[2]  S. P. Fodor,et al.  Large-Scale Transcriptional Activity in Chromosomes 21 and 22 , 2002, Science.

[3]  P. Sigler,et al.  A Model for Arrestin’s Regulation: The 2.8 Å Crystal Structure of Visual Arrestin , 1999, Cell.

[4]  W. Baehr,et al.  Identification of a nonsense mutation in the rod photoreceptor cGMP phosphodiesterase beta-subunit gene of the rd mouse. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  L. Wagner,et al.  21. UniGene: A Unified View of the Transcriptome , 2003 .

[6]  Erez Y. Levanon,et al.  Widespread occurrence of antisense transcription in the human genome , 2003, Nature Biotechnology.

[7]  D. Garbers,et al.  Two membrane forms of guanylyl cyclase found in the eye. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  I. Nir,et al.  S-antigen in rods and cones of the primate retina: different labeling patterns are revealed with antibodies directed against specific domains in the molecule. , 1992, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  Tiansen Li,et al.  Rootletin, a novel coiled-coil protein, is a structural component of the ciliary rootlet , 2002, The Journal of cell biology.

[10]  G. Lanfranchi,et al.  A two-step strategy for constructing specifically self-subtracted cDNA libraries. , 2002, Nucleic acids research.

[11]  K. Hofmann,et al.  Arrestin and Its Splice Variant Arr1–370A(p44) , 2002, The Journal of Biological Chemistry.

[12]  J. Ohlrogge,et al.  Microarray analysis of developing Arabidopsis seeds. , 2000, Plant physiology.

[13]  Tiansen Li,et al.  Retinal degeneration in the rd mouse is caused by a defect in the β subunit of rod cGMP-phosphodiesterase , 1990, Nature.

[14]  S. Cawley,et al.  Unbiased Mapping of Transcription Factor Binding Sites along Human Chromosomes 21 and 22 Points to Widespread Regulation of Noncoding RNAs , 2004, Cell.

[15]  D. Garbers,et al.  Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina. , 1996, Genomics.

[16]  A. Kerlavage,et al.  Complementary DNA sequencing: expressed sequence tags and human genome project , 1991, Science.

[17]  H. Stöhr,et al.  EST mining of the UniGene dataset to identify retina-specific genes , 2001, Cytogenetic and Genome Research.

[18]  S. Jovanovich,et al.  Gene expression analysis in response to lung toxicants: I. Sequencing and microarray development. , 2004, American journal of respiratory cell and molecular biology.

[19]  Seth Blackshaw,et al.  Comprehensive Analysis of Photoreceptor Gene Expression and the Identification of Candidate Retinal Disease Genes , 2001, Cell.

[20]  K. Palczewski,et al.  Phototransduction: crystal clear. , 2003, Trends in biochemical sciences.

[21]  Fuad G. Gwadry,et al.  Comparing cDNA and oligonucleotide array data: concordance of gene expression across platforms for the NCI-60 cancer cells , 2003, Genome Biology.

[22]  Guoying Liu,et al.  NetAffx: Affymetrix probesets and annotations , 2003, Nucleic Acids Res..

[23]  X. Mu,et al.  Gene expression in the developing mouse retina by EST sequencing and microarray analysis. , 2001, Nucleic acids research.

[24]  Graeme Wistow,et al.  A project for ocular bioinformatics: NEIBank. , 2002, Molecular vision.

[25]  T. Dryja,et al.  Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Farber,et al.  The β subunit of cyclic GMP phosphodiesterase mRNA is deficient in canine rod-cone dysplasia 1 , 1992, Neuron.

[27]  K. Martin,et al.  Identifying expressed genes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  L. Gan,et al.  Identification of Cathepsin B as a Mediator of Neuronal Death Induced by Aβ-activated Microglial Cells Using a Functional Genomics Approach* , 2004, Journal of Biological Chemistry.

[29]  Yoshihide Hayashizaki,et al.  Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. , 2003, Genome research.

[30]  G. Tsujimoto,et al.  Pregnancy-associated changes in genome-wide gene expression profiles in the liver of cow throughout pregnancy. , 2004, Biochemical and biophysical research communications.

[31]  M. Tomita,et al.  Identification of putative noncoding RNAs among the RIKEN mouse full-length cDNA collection. , 2003, Genome research.

[32]  J. Benovic,et al.  Mapping the Arrestin-Receptor Interface , 2004, Journal of Biological Chemistry.

[33]  Weiping Ma,et al.  Embryogenesis Microarray for Profiling Gene Expression Patterns during 15,000 Unique Zebrafish Est Clusters and Their Future Use in Material Supplemental , 2022 .

[34]  Yuqiu Jiang,et al.  Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays , 2002, Oncogene.

[35]  Yangrae Cho,et al.  Gene-expression profile comparisons distinguish seven organs of maize , 2002, Genome Biology.

[36]  J L Benovic,et al.  Visual arrestin interaction with rhodopsin. Sequential multisite binding ensures strict selectivity toward light-activated phosphorylated rhodopsin. , 1993, The Journal of biological chemistry.

[37]  J L Benovic,et al.  Cell-free expression of visual arrestin. Truncation mutagenesis identifies multiple domains involved in rhodopsin interaction. , 1992, The Journal of biological chemistry.

[38]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[39]  Thomas L Casavant,et al.  1274 full-open reading frames of transcripts expressed in the developing mouse nervous system. , 2004, Genome research.

[40]  C. Cepko,et al.  Profile of the genes expressed in the human peripheral retina, macula, and retinal pigment epithelium determined through serial analysis of gene expression (SAGE) , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Dizhoor,et al.  Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[42]  V. Gurevich,et al.  The molecular acrobatics of arrestin activation. , 2004, Trends in pharmacological sciences.

[43]  S. Daiger,et al.  Identifying and mapping novel retinal-expressed ESTs from humans. , 1999, Molecular vision.

[44]  E. Birney,et al.  Genome information resources - developments at Ensembl. , 2004, Trends in genetics : TIG.

[45]  P. Sigler,et al.  Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation. , 2001, Structure.

[46]  Gregory D. Schuler,et al.  ESTablishing a human transcript map , 1995, Nature Genetics.

[47]  S. Reed,et al.  Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. , 2000, Cancer research.

[48]  A. Hackam,et al.  Identification of novel genes preferentially expressed in the retina using a custom human retina cDNA microarray. , 2003, Investigative ophthalmology & visual science.

[49]  M. Soares,et al.  Normalization and subtraction: two approaches to facilitate gene discovery. , 1996, Genome research.

[50]  L. Rejtõ,et al.  Systems-wide chicken DNA microarrays, gene expression profiling, and discovery of functional genes. , 2003, Poultry science.

[51]  J. Inazawa,et al.  An expression profile of genes in human retina and isolation of a complementary DNA for a novel rod photoreceptor protein. , 1997, Investigative ophthalmology & visual science.

[52]  M. Tamai,et al.  A homozygous 1–base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese , 1995, Nature Genetics.

[53]  A. Milam,et al.  A splice variant of arrestin. Molecular cloning and localization in bovine retina. , 1994, The Journal of biological chemistry.

[54]  G. Tsujimoto,et al.  Global analysis of differentially expressed genes during progression of calcium oxalate nephrolithiasis. , 2002, Biochemical and biophysical research communications.

[55]  Jindan Yu,et al.  Mouse eye gene microarrays for investigating ocular development and disease , 2002, Vision Research.

[56]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[57]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[58]  Lixin Sun,et al.  Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury. , 2004, The Journal of clinical investigation.

[59]  Terence P Speed,et al.  The microarray: potential applications for ophthalmic research. , 2002, Molecular vision.

[60]  M. Soares,et al.  Identification and cloning of differentially expressed genes. , 1997, Current opinion in biotechnology.

[61]  P B Sigler,et al.  How Does Arrestin Respond to the Phosphorylated State of Rhodopsin?* , 1999, The Journal of Biological Chemistry.

[62]  C. Auffray,et al.  Gene expression profiling of human satellite cells during muscular aging using cDNA arrays. , 2003, Gene.

[63]  M. Akimoto,et al.  Gene microarray analysis of experimental glaucomatous retina from cynomologous monkey. , 2003, Investigative ophthalmology & visual science.

[64]  L. Ohno-Machado,et al.  Genomic Analysis of Mouse Retinal Development , 2004, PLoS biology.

[65]  K. Palczewski,et al.  Functional differences in the interaction of arrestin and its splice variant, p44, with rhodopsin. , 1997, Biochemistry.

[66]  S. Bortoluzzi,et al.  A novel resource for the study of genes expressed in the adult human retina. , 2000, Investigative ophthalmology & visual science.