May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Defective DOCK5 Signaling in Rupture of Lens Cataract in the Mouse
Author Affiliations & Notes
  • H. Hiai
    Shiga Med Ctr Res Inst, Shiga, Japan
  • N. Omi
    Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • E. Kiyokawa
    Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • Footnotes
    Commercial Relationships H. Hiai, None; N. Omi, None; E. Kiyokawa, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2446. doi:
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    • Get Citation

      H. Hiai, N. Omi, E. Kiyokawa; Defective DOCK5 Signaling in Rupture of Lens Cataract in the Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2446.

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

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Abstract

Purpose:: Rupture of lens cataract (RLC) in the mouse is inherited by a single autosomal recessive gene mapped on chromosome 14, featuring spontaneous rupture of lens at the posterior pole at 35 days of age or later. This study aims at positional cloning of the mutant gene to understand the lens pathology.

Methods:: The mutantlocus rlc was extensively mapped in 403 RLC x (RLC x MSM)F1 mice and the mutation gene was investigated by screening of RIKEN annotated full size cDNA collection. Nucleotide sequence, expression of mRNA as well as protein and localization of the protein were studied in mutant and wild type mice.

Results:: We identified a cDNA clone G270124C21Rik bearing a 27-bp nucleotide deletion, which was a partial sequence of Dock5 (Dedicator of cytokinesis-5), a member of the Dock gene superfamily. Since the deletion occurred in frame, the RLC-DOCK5 protein had a deletion of 9 amino acids (a.a. 506-514) in the DHR1 (DOCK homology region-1) domain that is essential for DOCK5 signaling. Immunohistochemically, DOCK5 was found in cytoplasm of the anterior epithelial cells in wild type, but little in RLC lens. The fact that Dock5 mRNA was detected both in mutant and wild type lenses suggests that the mutation may somehow destabilize DOCK5 protein. .

Conclusions:: Defective signaling by mutant DOCK5seemed responsible for the rupture of lens in RLC mice. We propose to designate the mutant allele rlc as Dock5rlc. This is the first report of an in vivo function of DOCK5.

Keywords: cataract • genetics • proteins encoded by disease genes 
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