Mouse Small eye results from mutations in a paired-like homeobox-containing gene

Abstract

Small eye (Sey) in mouse is a semidominant mutation which in the homozygous condition results in the complete lack of eyes and nasal primordia. On the basis of comparative mapping studies and on phenotypic similarities, Sey has been suggested to be homologous to congenital aniridia (lack of iris) in human. A candidate gene for the aniridia (AN) locus at 11p13 has been isolated by positional cloning and its sequence and that of the mouse homologue has been established (C.T., manuscript in preparation). This gene belongs to the paired-like class of developmental genes first described in Drosophila which contain two highly conserved motifs, the paired box and the homeobox. In vertebrates, genes which encode the single paired domain as well as those which express both motifs have been described as the Pax multigene family. A Pax gene recently described as Pax-6 is identical to the mouse homologue of the candidate aniridia gene. Here we report the analysis of three independent Sey alleles and show that indeed this gene is mutated and that the mutations would predictably interrupt gene function.

Pax6 is misexpressed in Sox1 null lens fiber cells

“…Pax6 is upstream of Sox2 (Furuta and Hogan, 1998), Pax6 and Sox2 cooperatively regulate gene expression (Kamachi et al 2001, Aota et al, 2003, and Sox2 is required for the maintenance of Pax6 (Donner et al, in press). Appropriate temporal, spatial, and quantitative control of Pax6 expression is required for appropriate lens morphogenesis (Hill et al, 1991;Glaser et al, 1994;Hanson et al, 1994;Grindley et al, 1995;Quinn et al, 1996;Schedl et al, 1996;Brown et al, 1998;Ashery-Padan et al, 2000;Duncan et al, 2000;van Raamsdonk and Tilgham, 2000;Dimanlig et al, 2001;Duncan et al, 2004). PAX6 mutation is causative for several congenital eye defects in humans including aniridia, Peters' anomaly and cataract (reviewed in Prosser and van Heyningen, 1998).…”

Expression of the Vax family homeobox genes suggests multiple roles in eye development

“…Their products are believed to regulate the expression of target genes during embryogenesis, several being detected in the developing eye (Pax6, Walther & Gruss 1991;Rx, Mathers et al 1997;Lhx2, Xu et al 1993;Chx10, Liu et al 1994). A direct participation of these genes in eye development has also been demonstrated using mutant and/or knockout mice (Sey, Hill et al 1991;Rx, Mathers et al 1997;Lhx2, Porter et al 1997;or, Burmeister et al 1996).…”

Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells

“…Finally, the genetical basis of the development of the eye-like structures was investigated by using ES cell lines established from the embryos of a Pax6 mutant (Pax6 Sey , Hill et al, 1991) in which eye structures are absent in the homozygote (Fig. 4C, shown as Pax6-/-).…”