Purpose: Vision is critically dependent on genetic factors that influence the rate and duration of eye growth. The genetic basis of variation in eye size in mice was explored, and genes that modulate eye weight, lens weight, and retinal area were mapped.
Methods: Eyes of approximately 700 mice were weighed. Data were corrected by regression analysis to eliminate effects of sex, age, and body weight. Interval mapping was used to locate quantitative trait loci (QTLs) using recombinant inbred strains and F2 intercrosses between strains C57BL/6J and DBA/2J.
Results: Major QTLs were discovered near the centromere of chromosome 5 (Eye1: genomewide P < 0.005) and on proximal chromosome 17 near the mast cell protease 6 gene (Eye2, P < 0.05). Both QTLs have significant effects on eye size, lens weight, and retinal area. The DBA/2J alleles at Eye1 and Eye2 are partially dominant and increase eye weight by as much as 1.0 mg. Analysis of 183 F2 progeny confirmed and refined the chromosomal assignments of both Eye1 and Eye2.
Conclusions: Eye1 and Eye2 are the first loci known to control normal variation in eye size in any mammal. The hepatic growth factor gene (Hgf), a potent mitogen expressed in the retina, pigment epithelium, and choroid, is a strong candidate for Eye1. The human homolog of Eye2 should map to chromosome 6p, 16q13.3, or 19q13, whereas that of Eye1 should map to 7q.