June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Identification of Novel Genes Required for Eye Function via Systematic Screening of Knockout Mouse Lines by the International Mouse Phenotyping Consortium
Author Affiliations & Notes
  • Ala Moshiri
    Ophthalmology, U.C. Davis, Sacramento, California, United States
  • Bret Moore
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
  • Ann Cooper
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
  • Brian Leonard
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
  • Sydney Edwards
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
  • Lionel Sebbag
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
  • Denise Imai
    Comparative Pathology Laboratory, U.C. Davis, Davis, California, United States
  • Stephen M. Griffey
    Comparative Pathology Laboratory, U.C. Davis, Davis, California, United States
  • David Clary
    Mouse Biology Program, UC Davis, Davis, California, United States
  • Lynette R Bower
    Mouse Biology Program, UC Davis, Davis, California, United States
  • Sara M Thomasy
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
  • Terrence Meehan
    International Mouse Phenotyping Program, European Bioinformatics Institute, Hinxton, Cambridgeshire, United Kingdom
  • Michel J Roux
    PHENOMIN-Institut Clinique de la Souris, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Strasbourg, France
  • Patrick Reilly
    PHENOMIN-Institut Clinique de la Souris, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Strasbourg, France
  • Yann Herault
    PHENOMIN-Institut Clinique de la Souris, Institut de Genetique et de Biologie Moleculaire et Cellulaire, Strasbourg, France
  • Christopher J Murphy
    Veterinary Surgical and Radiological Sciences, UC Davis, Davis, California, United States
    Ophthalmology, U.C. Davis, Sacramento, California, United States
  • Footnotes
    Commercial Relationships   Ala Moshiri, None; Bret Moore, None; Ann Cooper, None; Brian Leonard, None; Sydney Edwards, None; Lionel Sebbag, None; Denise Imai, None; Stephen Griffey, None; David Clary, None; Lynette Bower, None; Sara Thomasy, None; Terrence Meehan, None; Michel Roux, None; Patrick Reilly, None; Yann Herault, None; Christopher Murphy, None
  • Footnotes
    Support  RPB Career Development Award, International Retina Foundation Career Development Award
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3426. doi:
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      Ala Moshiri, Bret Moore, Ann Cooper, Brian Leonard, Sydney Edwards, Lionel Sebbag, Denise Imai, Stephen M. Griffey, David Clary, Lynette R Bower, Sara M Thomasy, Terrence Meehan, Michel J Roux, Patrick Reilly, Yann Herault, Christopher J Murphy; Identification of Novel Genes Required for Eye Function via Systematic Screening of Knockout Mouse Lines by the International Mouse Phenotyping Consortium. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3426.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To identify genes required for normal ocular development and function. Determining the genetic basis of eye development and function remains a major challenge in the diagnosis and treatment of both common and rare blinding diseases. This process requires a spectrum of approaches from human clinical genetics to the utilization of model organisms to direct scientists to potential disease loci. In this manuscript we report a large-scale genetic screen in mice using a phenotype-driven discovery strategy to identify genes required for normal eye function.

Methods : Forward systematic ophthalmic screening of single-gene targeted knockout mouse pipelines across several international sites to pinpoint genes required for various components of ocular anatomy and function. We performed complete ocular examination of all knockout mice produced at the Mouse Biology Program at UC Davis. To maximize the ocular phenotypes detected through all collaborative branches of this knockout mouse project, we interrogated the public data base at www.mousephenotype.org to include all animals with eye related phenotypes.

Results : In summary, we have identified 470 unique genes required for eye development and function. Of these, 308 have no known role in the eye in any species, and are therefore novel. Another 104 genes are known to be expressed in ocular tissues, but are not associated with a known ocular phenotype. The remaining 58 genes have established ocular phenotypes in humans, mice, fish, or other vertebrates. Each of these genes affects one or more ocular structures. The genes have been organized based on the structure(s) affected in the eye.

Conclusions : These genes reveal a number of new molecular pathways potentially involved in human ocular development and disease. We illustrate examples of knockout mouse phenotypes discovered in the screen affecting various compartments of the eye.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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