May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Genetic Modifiers of rd3 Retinal Degeneration
Author Affiliations & Notes
  • M. Danciger
    Biology, Loyola Marymount University, Los Angeles, California
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • D. Ogando
    Biology, Loyola Marymount University, Los Angeles, California
  • H. Yang
    Beckman Vision Center, UCSF, San Francisco, California
  • K. C. Ahern
    Beckman Vision Center, UCSF, San Francisco, California
  • N. Akhmedov
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • J. S. Friedman
    Ophthalmology & Visual Sciences,
    University of Michigan, Ann Arbor, Michigan
  • A. Swaroop
    Ophthalmology & Visual Sciences and Human Genetics,
    University of Michigan, Ann Arbor, Michigan
    Nei, NIH, Bethesda, Maryland
  • R. W. Williams
    Anatomy and Neurobiology, University of Tennessee, Memphis, Tennessee
  • D. B. Farber
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • M. M. LaVail
    Beckman Vision Center, UCSF, San Francisco, California
  • Footnotes
    Commercial Relationships  M. Danciger, None; D. Ogando, None; H. Yang, None; K.C. Ahern, None; N. Akhmedov, None; J.S. Friedman, None; A. Swaroop, None; R.W. Williams, None; D.B. Farber, None; M.M. LaVail, None.
  • Footnotes
    Support  NIH Grants EY013280, EY01919, EY02162; FFB; RPB
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 6081. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M. Danciger, D. Ogando, H. Yang, K. C. Ahern, N. Akhmedov, J. S. Friedman, A. Swaroop, R. W. Williams, D. B. Farber, M. M. LaVail; Genetic Modifiers of rd3 Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6081. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Previously, we identified several QTL that significantly modify the course of retinal degeneration in 431 10-week F2 progeny of an F1 intercross between B6(Cg)-Tyrc-2J/J (B6a) and BALB/cByJ (BALB) albino mice that are both congenic and homozygous for the rd3 allele. The purpose of this work was to refine the loci of the two strongest QTL at Chrs 17 and 5, and to evaluate candidate genes.

Methods: : Utilizing genomic DNAs from the original 431 F2 mice, the Center for Inherited Disease Research genotyped a number of SNPs in each QTL in a follow-up study. The data was analyzed with the Map Manager QTX program. A yeast two-hybrid (Y2H) screen of 1 x 106 transformed colonies from a human retina cDNA library was used to identify proteins interacting with RD3. Candidate genes were sequenced by standard methods and measured for expression by QPCR.

Results: : The Chr 17 QTL was reduced from ~40 Mb in the original map to a 1-LOD critical area of 16 Mb in the follow-up study utilizing 34 informative SNPs; the Chr 5 QTL from 23.5 to 9 Mb with 12 informative SNPs. The Y2H study revealed a non-redundant set of 41 cDNAs. Of these, two encoded genes that were orthologs of mouse genes in the Chr 17 critical area - Ppt2 and Hnrpm. Sequencing revealed no differences in the coding regions of either gene between the B6a and BALB strains. There was 1 sequence variant in the 3’ UTR of Hnrpm. The Crybb2 gene mapping to the reduced Chr 5 QTL was selected for study because of expression differences associated with retinal degeneration cited in the literature. There were no coding region differences in the cDNAs between the two strains. QPCR of the three candidate genes in B6a- and BALB-rd3/rd3 at 5 and 10 weeks showed a few differences but none were remarkable.

Conclusions: : Significant differences in expression or coding sequence between the B6a- and BALB-rd3/rd3 strains were not found in the three candidate genes studied so far. Other genes will be selected for future study based on function and implication in photoreceptor degeneration, but the critical areas of the QTL must be refined further by recombinant progeny testing to reduce the number of candidate genes.

Keywords: degenerations/dystrophies • gene modifiers • retina: distal (photoreceptors, horizontal cells, bipolar cells) 
×
×

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.

×