May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
RP1L1 Is Required for Appropriate Outer Segment Formation
Author Affiliations & Notes
  • J. Zuo
    Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN
  • J. Liu
    Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN
  • T. Yamashita
    Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN
  • R. Griffith
    Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN
    Biology Department, Christian Brothers University, Memphis, TN
  • A. Romeo
    Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN
  • S.J. Bowne
    Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science, The University of Texas–Houston Health Science Center, Houston, TX
  • S.P. Daiger
    Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science, The University of Texas–Houston Health Science Center, Houston, TX
  • L.S. Sullivan
    Human Genetics Center, School of Public Health, and Department of Ophthalmology and Visual Science, The University of Texas–Houston Health Science Center, Houston, TX
  • M.E. C. Fitzgerald
    Biology Department, Christian Brothers University, Memphis, TN
    Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN
  • Footnotes
    Commercial Relationships  J. Zuo, None; J. Liu, None; T. Yamashita, None; R. Griffith, None; A. Romeo, None; S.J. Bowne, None; S.P. Daiger, None; L.S. Sullivan, None; M.E.C. Fitzgerald, None.
  • Footnotes
    Support  NIH Cancer Center Support grant CA21765, the American Lebanese Syrian Associated Charities (ALSAC) and NIH grant EY12950, EY07142. ARVO/Japan National Society, Fight for Sight Fellowship
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4749. doi:
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      J. Zuo, J. Liu, T. Yamashita, R. Griffith, A. Romeo, S.J. Bowne, S.P. Daiger, L.S. Sullivan, M.E. C. Fitzgerald; RP1L1 Is Required for Appropriate Outer Segment Formation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4749.

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

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Abstract

Purpose: : Retinitis pigmentosa 1 (RP1) is a microtubule–associated protein specific for photoreceptors. An RP1–like protein, RP1L1, shares homology with RP1 only at its N–terminus to the DCX domain known as a microtubule–binding domain, and an adjacent 34–amino acid segment. Both RP1 and RP1L1 are specifically expressed in photoreceptors in similar temporal patterns. We hypothesized that RP1L1 is a microtubule–associated protein and involved in outer segment formation. To investigate the function of RP1L1, and potential interactions between RP1 and RP1L1, we created and characterized Rp1L1 knockout mice.

Methods: : We raised polyclonal antibodies against the C–terminal recombinant Rp1L1 protein in rabbits. Using ES cells, we targeted Rp1L1 in mice by deleting exons 2, 3, and a large portion of exon 4. Eyes from Rp1L1 knockout mice and wildtype littermates were collected at 1, 3, and 6 months of age for TEM, Western blot, and immunostaining analyses.

Results: : Western blot analysis using Rp1L1 antibodies demonstrated that Rp1L1 encodes a 200–kD protein in mouse retinas. Genomic Southern blot and real–time RT–PCR analyses confirmed the deletion of correct Rp1L1 exons and the absence of retinal Rp1L1 mRNA in homozygous mutant mice. Rp1L1–/– mice were viable. Light microscopy and TEM analyses of retinas of F2 mice at 1 and 6 months revealed that a small percentage of photoreceptors of Rp1L1–/– mice displayed abnormal outer segments (OS). Distal and middle portions of individual OS became enlarged, disoriented and disintegrated while surrounded by normal OS; some inner segments and nuclei of photoreceptors that were associated with degenerating OS were also degenerating. At 6 months, only one or two rows of photoreceptors have degenerated in Rp1L1–/– mice.

Conclusions: : Preliminary analyses showed that similar to RP1, RP1L1 is required for outer segment formation. The retinas of Rp1L1–/–mice displayed less severe and slightly different phenotypes that those of Rp1–/– mice. Additional experiments are in progress to refine the subcellular localization of RP1L1 and its interactions with RP1.

Keywords: photoreceptors • retina • degenerations/dystrophies 
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