Homozygous Deletion in the Coding Sequence of the c-mer Gene in RCS Rats Unravels General Mechanisms of Physiological Cell Adhesion and Apoptosis

Emeline Nandrot (1) , Eric Dufour (1) , Alexandra C Provost (1) , Marie O Péquignot (1) , Sébastien Bonnel (1) , Karïn Gogat (1) , Dominique Marchant (1) , Christelle Rouillac (1) , Bertille Sépulchre de Condé (1) , Marie-Thérèse Bihoreau (2) , Cindi Shaver , Jean-Louis Dufier (1) , Cécile Marsac (1) , Mark Lathrop (3) , Maurice Menasche (1) , Marc M Abitbol (1)

1 CERTO - Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie
2 The Wellcome Trust Centre for Human Genetics [Oxford]
3 GENOSCOPE - Genoscope - Centre national de séquençage [Evry]

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.

Mots clés: RCS rats; retinal pigment epithelium; macrophages; phagocytosis; c-mer; apoptosis; RCS rats

Domaines: Organes des sens

Emeline Nandrot, Eric Dufour, Alexandra C Provost, Marie O Péquignot, Sébastien Bonnel, et al.. Homozygous Deletion in the Coding Sequence of the c-mer Gene in RCS Rats Unravels General Mechanisms of Physiological Cell Adhesion and Apoptosis. Neurobiology of Disease, 2000, 7, pp.586 - 599. ⟨10.1006/nbdi.2000.0328⟩. ⟨hal-03086817⟩