A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene

doi:10.1073/pnas.0907720106

A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene

^aThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609;
^bMolecular Genetics Laboratory and
^gExperimental Ophthalmology, Centre for Ophthalmology, University Clinics Tübingen, Röntgenweg 11, D-72076 Tübingen, Germany;
^cUniversity Eye Hospital Essen, Hufelandstrasse 55, D-45122 Essen, Germany;
^dDepartment of Ophthalmology, Hacettepe University, Sihhiye-Ankara 06100, Turkey;
^eDepartment of Ophthalmology, University Hospital of Lund, 221 85 Lund, Sweden;
^fCentre de référence pour les Affections Rare en Génétique Ophthalmologique, Hôpitaux Universitaires de Strasbourg, 1 place de l'Hôpital, 67000 Strasbourg, France;
^hDepartment of Molecular Physiology and Biophysics, University of Iowa College of Medicine, 51 Newton Road, Iowa City, IA 52242-1109; and
ⁱKellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105

Edited by Jeremy Nathans, Johns Hopkins University School of Medicine, Baltimore, MD, and approved September 25, 2009 (received for review July 10, 2009)

Abstract

Retinal cone photoreceptors mediate fine visual acuity, daylight vision, and color vision. Congenital hereditary conditions in which there is a lack of cone function in humans cause achromatopsia, an autosomal recessive trait, characterized by low vision, photophobia, and lack of color discrimination. Herein we report the identification of mutations in the PDE6C gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase as a cause of autosomal recessive achromatopsia. Moreover, we show that the spontaneous mouse mutant cpfl1 that features a lack of cone function and rapid degeneration of the cone photoreceptors represents a homologous mouse model for PDE6C associated achromatopsia.

Footnotes

¹To whom correspondence should be addressed. E-mail: wissinger{at}uni-tuebingen.de
Author contributions: N.A., S.K., J.H., and B.W. designed research; B.C., T.G., S.D., R.H., B.J., E.C.S., S.A., H.D., B.B., S.B., and B.W. performed research; B.C., T.G., B.J., E.C.S., S.A., H.D., N.A., S.K., J.H., and B.W. analyzed data; and B.W. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0907720106/DCSupplemental.