June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Identification of Candidate Ciliopathy Genes by Genome-wide Screening of Knockout Mice with Ocular and Renal Phenotypes
Author Affiliations & Notes
  • Ala Moshiri
    Ophthalmology, U.C. Davis, Sacramento, California, United States
  • Kendall Higgins
    U. Miami School of Medicine, Miami, Florida, United States
  • Bret Moore
    UC Davis School of Veterinary Medicine , California, United States
  • Denise Imai
    UC Davis School of Veterinary Medicine , California, United States
  • Dave Clary
    UC Davis Mouse Biology Program, California, United States
  • KC Kent Lloyd
    UC Davis Mouse Biology Program, California, United States
  • Colin McKerlie
    The Hospital for Sick Children, Ontario, Canada
    The Centre for Phenogenomics, Ontario, Canada
  • Hibret Adissu
    The Centre for Phenogenomics, Ontario, Canada
  • Zorana Berberovic
    The Centre for Phenogenomics, Ontario, Canada
    Lunenfeld-Tanenbaum Research Institute, Ontario, Canada
  • Mohammed Eskandarian
    The Centre for Phenogenomics, Ontario, Canada
    Lunenfeld-Tanenbaum Research Institute, Ontario, Canada
  • Ann Flenniken
    The Centre for Phenogenomics, Ontario, Canada
    Lunenfeld-Tanenbaum Research Institute, Ontario, Canada
  • Susan Newbigging
    The Centre for Phenogenomics, Ontario, Canada
    Lunenfeld-Tanenbaum Research Institute, Ontario, Canada
  • Lauryl Nutter
    The Hospital for Sick Children, Ontario, Canada
    The Centre for Phenogenomics, Ontario, Canada
  • Footnotes
    Commercial Relationships   Ala Moshiri, None; Kendall Higgins, None; Bret Moore, None; Denise Imai, None; Dave Clary, None; KC Kent Lloyd, None; Colin McKerlie, None; Hibret Adissu, None; Zorana Berberovic, None; Mohammed Eskandarian, None; Ann Flenniken, None; Susan Newbigging, None; Lauryl Nutter, None
  • Footnotes
    Support  NIH NEI K08-EY027463
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1286. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ala Moshiri, Kendall Higgins, Bret Moore, Denise Imai, Dave Clary, KC Kent Lloyd, Colin McKerlie, Hibret Adissu, Zorana Berberovic, Mohammed Eskandarian, Ann Flenniken, Susan Newbigging, Lauryl Nutter; Identification of Candidate Ciliopathy Genes by Genome-wide Screening of Knockout Mice with Ocular and Renal Phenotypes. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1286.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Identify candidate ciliopathy genes by enriching all single gene knockout mouse strains produced by the International Mouse Phenotyping Consortium (IMPC) with both renal and eye abnormalities.

Methods : The IMPC database, containing comprehensive phenotypic data for over 7000 targeted deletions, was interrogated for all single gene knockout mice with abnormal renal phenotypes. These mice were cross-referenced individually to enrich for knockouts with concomitant ocular abnormalities. The targeted genes responsible for these phenotypes were analyzed for putative protein function using bioinformatic tools to predict interactions with known ciliary proteins.

Results : The IMPC database included 175 unique single gene knockout strains with kidney morphology abnormalities which were scrutinized for concomitant ocular abnormalities. We discovered 43 of 175 had ocular phenotypes. Thirty-four of these 43 'oculorenal genes' are novel. Bioinformatic analysis suggests 6 are candidate ciliopathy genes based on predicted interactions with established ciliopathy genes. Two additional candidate ciliopathy genes were identified by including knockouts with abnormal renal function identified by plasma BUN and/or Creatinine.

Conclusions : Here we present targeted deletions of 147 genes previously unknown to cause renal abnormalities, 34 of which represent novel oculorenal disease genes in mice, and 8 that represent candidate ciliopathy genes.

This is a 2020 ARVO Annual Meeting abstract.

 

Protein network interactions of putative ciliopathy genes and known ciliopathy genes. A STRING interaction map of known ciliopathy genes with putative ciliopathy from mice having both abnormal kidney and eye phenotypes. Proteins are shown as nodes on the map where green is indicative of a putative ciliopathy gene and purple shown known ciliopathy genes. Each line represents a STRING interaction score of greater than or equal to .9 based on 5 pieces of evidence: “experiments,’’ ‘‘databases,’’ ‘‘co-expression,’’ ‘‘neighborhood,’’ ‘‘gene fusion,’’ and ‘‘co- occurrence.’’ Five genes of the 43 are shown to be interacting with known ciliopathy genes. Each of the 5 interacting oculorenal genes were analyzed for functional enrichment with their primary interacting proteins. Labeled with number 1-5 and encompassed by shaded box. The corresponding highlighted term reflects cellular components known to be related to either ciliary structure, function, or maintenance

Protein network interactions of putative ciliopathy genes and known ciliopathy genes. A STRING interaction map of known ciliopathy genes with putative ciliopathy from mice having both abnormal kidney and eye phenotypes. Proteins are shown as nodes on the map where green is indicative of a putative ciliopathy gene and purple shown known ciliopathy genes. Each line represents a STRING interaction score of greater than or equal to .9 based on 5 pieces of evidence: “experiments,’’ ‘‘databases,’’ ‘‘co-expression,’’ ‘‘neighborhood,’’ ‘‘gene fusion,’’ and ‘‘co- occurrence.’’ Five genes of the 43 are shown to be interacting with known ciliopathy genes. Each of the 5 interacting oculorenal genes were analyzed for functional enrichment with their primary interacting proteins. Labeled with number 1-5 and encompassed by shaded box. The corresponding highlighted term reflects cellular components known to be related to either ciliary structure, function, or maintenance

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×