Eye development is severely disrupted in Raxey1 homozygotes resulting in anophthalmia in most instances and microphthalmia where eyes do form. There are likely multiple modifiers impacting the severity of phenotype in this strain. Harch et al (1978) reported finding approximately 70% anophthalmia and 30% microphthalmia in Raxey1 homozygotes whereas Piche et al (2004) reported approximately 90% anophthalmia and 10% microphthalmia in a small sample population. Anophthalmic mice have orbits and eyelids but lack eyes and optic tracts (Chase et al. 1941). Microphthalmic mice have one or two small eyes, and may have an optic nerve (Chase et al. 1941). The phenotype is first distinguished at approximately embryonic day ten. Optic vesicles develop, however, they are reduced in size and contact poorly with surface ectoderm (Chase et al. 1941). A normal eyed control strain, ZRDCT Rax+/ChUmdJ (Stock No. 005005) was developed in parallel with ZRDCT Raxey1. Raxey1 mice exhibit an abnormal hypothalmus (Silver 1977) and altered circadian rhythm (Laemle et al. 1998). This strain serves as a model for human anophthalmia.
ZRDCT Raxey1 and ZRDCT Rax+ mice were developed from the anophthalmic strain B described by Chase in 1941. The original animals from strain R were obtained from Little at The Jackson Laboratory in 1938. Little selectively bred for anophthalmia by sibling matings, Chase continued the inbreeding to 21+ generations. Two sublines were established designated Be1 for the 98% eyeless group (Raxey1) and Be2 for the 96% normal group (Rax+) (Chase 1944). The donating investigator, Dr. Lois Laemle, indicates that this strain came from Chase through Dr. Kaiserman-Abramof. This strain did not come from Dr. Sidney Beck. It is not clear when the designation ZRDCT appeared. The strain was donated to The Jackson Laboratory in 2004.
|Allele Name||eyeless 1|
|Allele Synonym(s)||An; anophthalmia; anophthalmic; ey; ey1; ZRDCT-An|
|Gene Symbol and Name||Rax, retina and anterior neural fold homeobox|
|Strain of Origin||ZRDCT/Ch|
|Molecular Note||An A-to-T transversion at coding nucleotide 28 (c.28A>T) results in a methionine to leucine amino acid substitution at position 10 of the encoded protein (p.M10L). The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of protein. The mutation does not destabilize mRNA.|