Rho GTPase inactivation impairs lens growth and integrity.

Published

Journal Article

To elucidate the significance of Rho GTPase signaling on lens growth and structural integrity, we have selectively inactivated Rho GTPase in the ocular lens. To achieve this tissue-specific inactivation, a transgene encoding the C3-exoenzyme from Clostridium botulinum has been expressed in mice under transcriptional control of the lens-specific alphaA-crystallin promoter. C3-exoenzyme is known to selectively inactivate all Rho GTPase isoforms by ADP-ribosylating an asparagine residue at position 41. Mice expressing the C3-exoenzyme transgene exhibited selective ocular defects, including cataract and microphthalmia. Extralenticular effects included ocular hemorrhage (blood accumulation in the anterior and posterior chambers of the eye) and abnormalities of the iris including focal attachments to lens and cornea (synechiae). C3-transgene expression was found only in the lens and not in the other ocular tissues as determined by RT-PCR analysis. Histologic examination of the eyes of C3 transgenic mice from two independent lines revealed extensive abnormalities of the lens, including defective fiber cell differentiation and elongation, ruptured posterior lens capsule, and thickened anterior lens capsule. Electron microscopic analysis of hemorrhaged C3 eyes showed abnormalities in the posterior hyaloid vessels. Collectively these data reveal the importance of Rho GTPase signaling in regulating lens growth and maintenance of lens transparency.

Full Text

Duke Authors

Cited Authors

  • Rao, V; Wawrousek, E; Tamm, ER; Zigler, S

Published Date

  • February 2002

Published In

Volume / Issue

  • 82 / 2

Start / End Page

  • 231 - 239

PubMed ID

  • 11850536

Pubmed Central ID

  • 11850536

Electronic International Standard Serial Number (EISSN)

  • 1530-0307

International Standard Serial Number (ISSN)

  • 0023-6837

Digital Object Identifier (DOI)

  • 10.1038/labinvest.3780415

Language

  • eng