Mechanisms of Embryonic Induction in Vertebrates 
lens results in formation of the anterior structures 
of the eye, specifically the iris, cornea, and ciliary 
body. An additional interaction, between the de- 
veloping lens and retina, is suggested by experi- 
ments involving transgenic mice: ablation of the 
developing lens results in an abnormal prolifera- 
tion of retina, perhaps suggesting the presence of 
an inhibitory factor from lens. 
In both mouse and human, there are naturally 
occurring mutations that affect eye development. 
In the mouse, a mutation on chromosome 2, 
called Small eye {Sey), results in deficient eye 
formation. The portion of mouse chromosome 2 
to which Sey maps is homologous to a portion of 
human chromosome 11, llpl3. Interestingly, a 
semidominant human disorder called aniridia, 
which also affects basic eye development, is lo- 
cated in this region of 1 1 . The observation that a 
mouse paired box and homeobox gene. Pax- 6, 
maps to the Sey locus prompted us to examine 
the role of this gene and its human counterpart in 
basic ocular development. Recently it has been 
shown that point mutations in the mouse Pax- 6 
gene are in fact responsible for the Sey mutation. 
We have cloned the human PAX6 gene, which 
maps to within 200 kb or less of the human ani- 
ridia locus, as defined by various translocation 
breakpoints. This gene is more than 95 percent 
conserved over 422 amino acids with a related 
gene cloned from zebra fish, which is expressed 
in both the diencephalon and lens vesicle during 
ocular development. Thus both the chromosomal 
location and the expression pattern of this gene 
are consistent with its involvement in aniridia. 
We have determined the genomic structure of 
the PAX6 gene, which consists of at least 13 
exons spread over some 30 kb of genomic DNA, 
and have sequenced the intron-exon boundaries. 
This has permitted the design of PGR primers to 
each exon, which are conveniently sized for anal- 
ysis by PGR. Thus far we have identified a non- 
sense mutation located in helix 2 of the homeo- 
box of the human PAX6 gene in one patient and, 
preliminarily, a small insertion in the PAX6 gene 
of another patient. Although analysis of more mu- 
tations will be required to establish that muta- 
tions in PAX6 indeed account for aniridia, these 
findings argue persuasively that they do. 
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