The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene

The eyeless inbred mouse strain ZRDCT has long served as a spontaneous mode l for human anophthalmia and the evolutionary reduction of eyes that has oc curred in some naturally blind mammals. ZRDCT mice have orbits but lack eye s and optic tracts and have hypothalamic abnormalities. Segregation data su ggest that a small number of interacting genes are responsible, including a t least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10 --> Leu mutation in Rx/rax, a homeob ox gene that is expressed in the anterior headfold, developing retina, pine al, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative tra nslation initiation site and consequently reduces the abundance of Rx prote in. In contrast to a targeted Rx null allele, which causes anophthalmia, ce ntral nervous system defects, and neonatal death, the hypomorphic M10L alle le is fully viable. (C) 2001 Wiley-Liss, Inc.