Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat

Patricia M. D'Cruz, Douglas Yasumura, Jessica Weir, Michael T. Matthes, Hadi Abderrahim, Matthew M. LaVail, Douglas Vollrath

Research output: Contribution to journalArticle

617 Citations (Scopus)

Abstract

Vertebrate photoreceptor cells are the basic sensory apparatus of the retina, capable of converting the energy of absorbed photons into neuronal signals. The proximal portions of mammalian photoreceptor outer segments are synthesized daily by cell bodies, and outer segment tips are shed with a circadian rhythm, resulting in a complete turnover of outer segments about every 9 days. The shed outer segments are phagocytosed by adjacent retinal pigment epithelial (RPE) cells, and metabolites are recycled to photoreceptors. The Royal College of Surgeons (RCS) rat is a widely studied, classic model of recessively inherited retinal degeneration in which the RPE fails to phagocytose shed outer segments, and photoreceptor cells subsequently die. We have used a positional cloning approach to study the rdy (retinal dystrophy) locus of the RCS rat. Within a 0.3 cM genetic inclusion interval, we have discovered a small deletion of RCS DNA that disrupts the gene encoding the receptor tyrosine kinase Mertk. The deletion includes the splice acceptor site upstream of the second coding exon of Mertk and results in a shortened transcript that lacks this exon. The aberrant transcript joins the first and third coding exons, leading to a frameshift and a translation termination signal 20 codons after the AUG. The concordance of these and other data indicate that Mertk is probably the gene for rdy. Our results provide genetic evidence for an essential role of a receptor tyrosine kinase in a specialized form of phagocytosis and suggest a molecular model for ingestion of outer segments by RPE cells.

Original languageEnglish
Pages (from-to)645-651
Number of pages7
JournalHuman Molecular Genetics
Volume9
Issue number4
Publication statusPublished - 1 Mar 2000
Externally publishedYes

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Retinal Pigments
Receptor Protein-Tyrosine Kinases
Phagocytosis
Retinal Dystrophies
Exons
Mutation
Epithelial Cells
Genes
Photoreceptor Cells
Retinal Degeneration
RNA Splice Sites
Vertebrate Photoreceptor Cells
Molecular Models
Circadian Rhythm
Photons
Codon
Retina
Organism Cloning
Eating
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

D'Cruz, P. M., Yasumura, D., Weir, J., Matthes, M. T., Abderrahim, H., LaVail, M. M., & Vollrath, D. (2000). Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Human Molecular Genetics, 9(4), 645-651.

Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. / D'Cruz, Patricia M.; Yasumura, Douglas; Weir, Jessica; Matthes, Michael T.; Abderrahim, Hadi; LaVail, Matthew M.; Vollrath, Douglas.

In: Human Molecular Genetics, Vol. 9, No. 4, 01.03.2000, p. 645-651.

Research output: Contribution to journalArticle

D'Cruz, PM, Yasumura, D, Weir, J, Matthes, MT, Abderrahim, H, LaVail, MM & Vollrath, D 2000, 'Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat', Human Molecular Genetics, vol. 9, no. 4, pp. 645-651.
D'Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM et al. Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Human Molecular Genetics. 2000 Mar 1;9(4):645-651.
D'Cruz, Patricia M. ; Yasumura, Douglas ; Weir, Jessica ; Matthes, Michael T. ; Abderrahim, Hadi ; LaVail, Matthew M. ; Vollrath, Douglas. / Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. In: Human Molecular Genetics. 2000 ; Vol. 9, No. 4. pp. 645-651.
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