1. Homozygous Deletion in the Coding Sequence of the c-mer Gene in RCS Rats Unravels General Mechanisms of Physiological Cell Adhesion and Apoptosis
- Author
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Jean-Louis Dufier, Maurice Menasche, Cécile Marsac, Eric M Dufour, Alexandra C. Provost, Marie-Thérèse Bihoreau, Sébastien Bonnel, Bertille Sépulchre de Condé, Christelle Rouillac, Cindi Shaver, Karïn Gogat, Emeline F. Nandrot, Marie O. Pequignot, Mark Lathrop, Marc Abitbol, Dominique Marchant, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Nandrot, Emeline, and University of Oxford [Oxford]
- Subjects
Candidate gene ,retinal pigment epithelium ,Receptor tyrosine kinase ,0302 clinical medicine ,Rats, Inbred BN ,Coding region ,Inbreeding ,Fluorescein Angiography ,Peptide sequence ,Sequence Deletion ,0303 health sciences ,biology ,Homozygote ,apoptosis ,Chromosome Mapping ,phagocytosis ,Protein-Tyrosine Kinases ,macrophages ,Phenotype ,Neurology ,Organ Specificity ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,RCS rats ,Genotype ,Molecular Sequence Data ,Genes, Recessive ,Locus (genetics) ,Rats, Mutant Strains ,lcsh:RC321-571 ,03 medical and health sciences ,Retinal Diseases ,Proto-Oncogene Proteins ,Cell Adhesion ,Electroretinography ,Animals ,Radiation hybrid mapping ,Amino Acid Sequence ,RNA, Messenger ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Gene ,Crosses, Genetic ,030304 developmental biology ,Base Sequence ,c-Mer Tyrosine Kinase ,GAS6 ,Receptor Protein-Tyrosine Kinases ,Sequence Analysis, DNA ,Molecular biology ,Rats ,c-mer ,biology.protein ,030217 neurology & neurosurgery - Abstract
International audience; The RCS rat presents an autosomal recessive retinal pigment epithelium dystrophy characterized by the outer segments of photoreceptors being phagocytosis-deficient. A systematic genetic study allowed us to restrict the interval containing the rdy locus to that between the markers D3Mit13 and D3Rat256. We report the chromosomal localization of the rat c-mer gene in the cytogenetic bands 3q35-36, based on genetic analysis and radiation hybrid mapping. Using a systematic biocomputing analysis, we identified two strong related candidate genes encoding protein tyrosine kinase receptors of the AXL subfamily. The comparison of their expression patterns in human and mice tissues suggested that the c-mer gene was the best gene to screen for mutations. RCS rdy؊ and RCS rdy؉ cDNAs were sequenced. The RCS rdy؊ cDNAs carried a significant deletion in the 5 part of the coding sequence of the c-mer gene resulting in a shortened aberrant transcript encoding a 20 amino acid peptide. The c-mer gene contains characteristic motifs of neural cell adhesion. A ligand of the c-mer receptor, Gas6, exhibits antiapoptotic properties.
- Published
- 2000