Microphthalmia and cataract in rats with a novel point mutation in connexin 50 - L7Q.

Abstract

PURPOSE:

We isolated an autosomal semi-dominant cataract from our inbred SHR/OlaIpcv rat colony. Heterozygotes express pulverulent cataract with smaller eyes; homozygotes express marked microphthalmia with hypoplastic lens. We call this mutation Dca (for dominant cataract). In this study, we focus on the identification of the responsible gene.

METHODS:

We performed linkage mapping using 93 F2(SHR-Dca x PD) hybrids and a panel of microsatellite markers. In a separate group of animals with a SHR genetic background, we examined the lenses histologically using Epon semi-thin sections and toluidine blue staining. We also assessed the weight of the eyes as an immediate measure for microphthalmia.

RESULTS:

We mapped the Dca gene to chromosome 2, spanning 8.6 Mbp between markers D2Rat134 and D2Rat186. By sequencing the most plausible candidate gene, Gja8 (coding for connexin 50), we found a T to A transversion at codon 7, leading to a substitution of glutamine for leucin (L7Q). L7Q lies within the NH(2)-terminal cytosolic domain, presumably involved in voltage gating. Histology revealed disturbances in cell to cell contacts in the lens.

CONCLUSIONS:

L7Q is a novel mutation in connexin 50 (Gja8), causing semi-dominant pulverulent cataracts. Dca rats can serve as a model for cataract development. A study on the properties of the mutant protein may offer an insight into the connexin channel function.

• Authors: Frantisek Liska, Blanka Chylíková, Jindrich Martínek, Vladimír Kren
• Journal: Molecular vision (Mol Vis) Vol. 14 Pg. 823-8 (May 07 2008) ISSN: 1090-0535 [Electronic] United States
• PMID: 18470322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Connexins
• Eye Proteins
• connexin 50
• Glutamine
• Lysine

Topics

• Amino Acid Sequence
• Amino Acid Substitution
• Animals
• Cataract (genetics, pathology)
• Chromosome Mapping
• Connexins (chemistry, genetics)
• Eye Proteins (chemistry, genetics)
• Glutamine (genetics)
• Inheritance Patterns (genetics)
• Lens, Crystalline (pathology)
• Lysine (genetics)
• Microphthalmos (genetics, pathology)
• Molecular Sequence Data
• Phenotype
• Point Mutation (genetics)
• Rats