April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Abnormal Ciliary Zonule Formation In Ltbp2 Knockout Mice
Author Affiliations & Notes
  • Tomoya O. Akama
    Kansai Medical University, Osaka, Japan
    Sanford-Burnham Medical Research Institute, La Jolla, California
  • Tadashi Inoue
    Kansai Medical University, Osaka, Japan
  • Tetsuya Ohbayashi
    Tottori University, Tottori, Japan
  • Masahito Horiguchi
    New York University, New York, New York
  • Kanji Takahashi
    Kansai Medical University, Osaka, Japan
  • Tomoyuki Nakamura
    Kansai Medical University, Osaka, Japan
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2353. doi:
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      Tomoya O. Akama, Tadashi Inoue, Tetsuya Ohbayashi, Masahito Horiguchi, Kanji Takahashi, Tomoyuki Nakamura; Abnormal Ciliary Zonule Formation In Ltbp2 Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2353.

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

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Abstract

Purpose: : Latent TGF-beta binding proteins (LTBPs) are extracellular matrix proteins that bind to small latent TGF-beta complex and are involved in TGF-beta signaling pathway in various tissues. Among the four LTBPs, LTBP2 is the only protein reported not to bind to the small latent TGF-beta complex, and suggested to have a different function from TGF-beta signaling. Previous gene targeting experiment demonstrated early embryonic lethality of Ltbp2-null mice, suggesting an indispensable function of LTBP2 in embryonic development of mice. In contrast to the report, recent studies revealed that human null mutations on LTBP2 lead to hereditary eye diseases, such as primary congenital glaucoma and ectopia lentis, and suggested important function of LTBP2 in the eye but not normal embryonic development in human. In this study, we have generated a new Ltbp2-knockout mouse line and analyzed the phenotype of the mutant mice.

Methods: : We generated Ltbp2 flox mice and crossed them with a germline-Cre deleter mouse line to produce Ltbp2-null mice. We investigated abnormalities and phenotypes in the homozygous mutant mice, especially in the eye, by immunohistological and electron microscopic analyses.

Results: : We obtained homozygous mutant mice, which have neither obvious macroscopic phenotype nor reproductive abnormality. By electron microscopic analysis, however, we observed fragmented ciliary zonules, which primarily consist of fibrillin proteins, in the eye of Ltbp2-mutant mice. We also confirmed presence of LTBP2 on ciliary zonules in addition to fibrillins in wild type mouse eyes, indicating unknown function of LTBP2 for formation and stabilization of ciliary zonules. We so far observed no phenotype that is related to glaucoma in the mutant mice.

Conclusions: : Our findings of abnormal ciliary zonule structure in Ltbp2-mutant mice correspond to the phenotypes found in some of the patients who have mutations on LTBP2. The results suggested functional importance of LTBP2 in ciliary zonule formation and possible association of the protein malfunction in development of glaucoma.

Keywords: extracellular matrix • ciliary processes • proteins encoded by disease genes 
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