International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

I2 The Identification and Characterization of Connexin 50 Mutations in the Mouse which Express Nuclear and Zonular Cataract

Jack Favor1, Rodica Sandulache1, Patricia Grimes2 and Angelika Neuhäuser-Klaus1. 1GSF-Institute of Mammalian Genetics, Neuherberg, Germany; 2Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

We have recovered and maintained an extensive series of dominant mutations expressing eye abnormalities in the mouse. The mutations are being mapped and, based on chromosomal location, we are attempting to identify the affected gene via a positional-candidate gene approach. To date, five independent mutations have been mapped to proximal chromosome 3 in the region of Gja8, the gene encoding connexin 50, a major component of the lens fiber cell gap junction. At present three mutations have been confirmed as Gja8 mutant alleles (Steele et al., Curr. Eye Res., 1998; present results). All three were induced by ENU, express as heterozygotes nuclear and zonular cataract and are nucleotide substitutions resulting in amino acid changes with charge modifications in different domains of the connexin 50 protein. Connexin 50 is expressed in the lens primary and secondary fibers. A sequence of steps involving Connexin 50 is important in proper lens fiber development including expression, localization to the plasma membrane, formation of the gap junctions and proteolytic processing of the membrane-bound Connexin 50 protein. Different domains of the Connexin 50 molecule may be important for the specific steps and an analysis of our mutations may be useful to elucidate the function of the different domains. These and other mouse mutations from our collection may be useful models for human hereditary ocular defects and their analysis should contribute to an understanding of the mechanisms of cataract development.

Research supported in part by NIH grant RO1EY10321.


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