BioSpace.com

Biotech and Pharmaceutical
News & Jobs
Search the Site
 
   
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Browse Biotech Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  US Device
Europe
Asia

DIVERSITY

INVESTOR
Market Summary
News
IPOs

PROFILES
Company Profiles

START UPS
Companies
Events

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Biotech Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Ophthalmology

Effects of Aberrant Pax6 Gene Dosage on Mouse Corneal Pathophysiology and Corneal Epithelial Homeostasis
Published: Thursday, December 29, 2011
Author: Richard L. Mort et al.

by Richard L. Mort, Adam J. Bentley, Francis L. Martin, J. Martin Collinson, Panagiotis Douvaras, Robert E. Hill, Steven D. Morley, Nigel J. Fullwood, John D. West

Background

Altered dosage of the transcription factor PAX6 causes multiple human eye pathophysiologies. PAX6+/- heterozygotes suffer from aniridia and aniridia-related keratopathy (ARK), a corneal deterioration that probably involves a limbal epithelial stem cell (LESC) deficiency. Heterozygous Pax6+/Sey-Neu (Pax6+/-) mice recapitulate the human disease and are a good model of ARK. Corneal pathologies also occur in other mouse Pax6 mutants and in PAX77Tg/- transgenics, which over-express Pax6 and model human PAX6 duplication.

Methodology/Principal Findings

We used electron microscopy to investigate ocular defects in Pax6+/- heterozygotes (low Pax6 levels) and PAX77Tg/- transgenics (high Pax6 levels). As well as the well-documented epithelial defects, aberrant Pax6 dosage had profound effects on the corneal stroma and endothelium in both genotypes, including cellular vacuolation, similar to that reported for human macular corneal dystrophy. We used mosaic expression of an X-linked LacZ transgene in X-inactivation mosaic female (XLacZTg/-) mice to investigate corneal epithelial maintenance by LESC clones in Pax6+/- and PAX77Tg/- mosaic mice. PAX77Tg/- mosaics, over-expressing Pax6, produced normal corneal epithelial radial striped patterns (despite other corneal defects), suggesting that centripetal cell movement was unaffected. Moderately disrupted patterns in Pax6+/- mosaics were corrected by introducing the PAX77 transgene (in Pax6+/-, PAX77Tg/- mosaics). Pax6Leca4/+, XLacZTg/- mosaic mice (heterozygous for the Pax6Leca4 missense mutation) showed more severely disrupted mosaic patterns. Corrected corneal epithelial stripe numbers (an indirect estimate of active LESC clone numbers) declined with age (between 15 and 30 weeks) in wild-type XLacZTg/- mosaics. In contrast, corrected stripe numbers were already low at 15 weeks in Pax6+/- and PAX77Tg/- mosaic corneas, suggesting Pax6 under- and over-expression both affect LESC clones.

Conclusions/Significance

Pax6+/- and PAX77Tg/- genotypes have only relatively minor effects on LESC clone numbers but cause more severe corneal endothelial and stromal defects. This should prompt further investigations of the pathophysiology underlying human aniridia and ARK.

  More...

 

//-->