Characterization of the mouse Prox1 gene

Area of Science:

• Genetics
• Developmental Biology
• Ophthalmology

Background:

• Prox1 is a divergent homeodomain protein and a vertebrate homologue of Drosophila prospero.
• The mouse Prox1 gene is located on Chromosome 1, near the retinal degeneration mutation, rd3.

Purpose of the Study:

• To isolate and characterize full-length mouse Prox1 cDNA and genomic clones.
• To investigate the relationship between the Prox1 gene and the rd3 mutation in mice.

Main Methods:

• Isolation and characterization of mouse Prox1 cDNA and genomic clones.
• Gene mapping of the mouse Prox1 gene.
• Northern blot analysis of Prox1 mRNA in wild type and rd3 mutant retinas.
• Immunostaining to analyze Prox1 protein distribution in wild type and rd3 mutant eyes.

Main Results:

• The mouse Prox1 gene was mapped to Chromosome 1 at 106.3 cM, near the rd3 mutation.
• Coding sequences and exon-intron junctions of Prox1 were identical in wild type and rd3 mutant mice.
• Differential ratios of short (2.3 kb) and long (8 kb) Prox1 mRNA forms were observed in rd3 mutant retinas compared to wild type.
• Distinct Prox1 protein distribution patterns were found in the retinas and lenses of rd3 mutant versus wild type animals.

Conclusions:

• The rd3 mutation does not alter the coding sequence or exon-intron structure of the Prox1 gene.
• The rd3 mutation appears to affect the expression levels or ratios of Prox1 mRNA isoforms.
• Differences in Prox1 protein distribution suggest the rd3 mutation impacts Prox1 gene regulation or function in the retina and lens.