AN AUTOSOMAL RECESSIVE MUTATION ON MOUSE CHROMOSOME 16 LEADING TO ANTERIOR RETINA INVERSION, CILIARY AGENESIS AND LOSS OF VITREOUS HUMOR

Quynh Duong

Abstract

PURPOSE. Much current understanding of basic mechanisms of eye development derives from studies of mutations that alter normal ocular developmental patterns. OVE401B is an autosomal recessive mutation resulting in microphthalmia that spontaneously arose in a transgenic mouse line. In subsequent generations, the mutant phenotype segregated away from the transgene suggesting that the mutation and transgenic insertion site were different genetic loci. Our purpose was to characterize the mutant phenotype and to map the genetic position of this mutation. METHOD. Age-matched eyes from mutant and wild-type mice were examined histologically. The location of the OVE401B mutation was determined by a backcross analysis. Backcross progeny were genotyped for polymorphic microsatellite markers distributed throughout the genome.

RESULTS. OVE401B mutant mice displayed disruptions in the differentiation of the anterior retina. In the FVB/N strain background, mutant animals demonstrated a complete lack of vitreous humor, abnormal ciliary body development, and inversion of the anterior retina. The phenotype on the backcross background was milder, but the anterior retina inversion was consistently observed in all mutant animals. A genetic screening of 96 backcross animals placed the mutation between markers D16Mit84 and D16Mit169, a position correspondent to human chromosome 3 q13. This interval encompasses roughly 7.5 X 106 bp.

CONCLUSIONS. OVE401B is a spontaneous autosomal recessive mutation on mouse chromosome 16 that results in microphthalmia. Mutant animals display an inversion of the anterior retina, fail to develop a morphologically normal ciliary body and suffer from abnormalities in the vitreous humor, lens and iris. Further work will focus on the identification of the mutated gene and the elucidation of that gene’s function in normal ocular development.

Details

Year: 2001

Program Number: Poster 139

Author Affiliation: The Ohio State University

Co-Authors: Christian Rizo, Michael Robinson

Co-Author Affiliation: Children''''s Research Institute, Children''''s Research Institute

Room: Exhibit Hall C