Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis.
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.
Nandrot
E
E
Université René Descartes, Centre de Recherches Thérapeutiques en Ophtalmologie, Paris, France.
Dufour
E M
EM
Provost
A C
AC
Péquignot
M O
MO
Bonnel
S
S
Gogat
K
K
Marchant
D
D
Rouillac
C
C
Sépulchre de Condé
B
B
Bihoreau
M T
MT
Shaver
C
C
Dufier
J L
JL
Marsac
C
C
Lathrop
M
M
Menasche
M
M
Abitbol
M M
MM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004596:Electroretinography; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D005838:Genotype; D006720:Homozygote; D007178:Inbreeding; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D020794:Receptor Protein-Tyrosine Kinases; D012164:Retinal Diseases / Q000209:etiology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*; D000076202:c-Mer Tyrosine Kinase
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C490765:Mertk protein, rat; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase