Small eyes (Sey) : a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse

Abstract

Small eyes (Sey) is a semidominant, homozygous lethal mutation in the mouse (Roberts, 1967). It is allelic with SeyH, a radiation-induced homozygous prenatal lethal which has been mapped on chromosome 2. The effect of the Sey mutation is apparently limited to the growth and differentiation of the presumptive lens and nasal placodes. Homozygous Sey /Sey embryos can be distinguished as early as 10·5 days post coitum (p.c); the optic vesicles grow out, but the ectoderm does not give rise to a lens and nasal pits never form. Immunohistochemical studies show that the distribution of the extracellular matrix glycoprotein laminin is not significantly different in the cephalic region of Sey/Sey versus Sey/+ or +/+ embryos. Sey/Sey embryos develop to term but without eyes or nose, and die soon after birth. Further analysis of Sey/Sey embryos may throw light on the mechanisms underlying morphogenesis of craniofacial structures in mammals.

PAX6 disease models for aniridia

“…Given the limited access to the human eye, animal and cellular disease models have been, and continue to be, crucial in identifying the genetics and pathophysiology underlying aniridia. [ 14 18 32 33 ] The function and structure of the mature eye is similar across different vertebrate species. [ 34 ] Animal models allow us to consider genotype–phenotype correlations, as well as potentiate the identification of molecular pathways of disease progression.…”

Cell fate decisions, transcription factors and signaling during early retinal development

“…Loss-of-function studies of Pax6 in mice were conducted using both somatic ( Hogan et al, 1986 ; Hill et al, 1991 ; Grindley et al, 1995 ; Quinn et al, 1996 ) and conditional mutants using different cre-lines ( Marquardt et al, 2001 ; Oron-Karni et al, 2008 ; Farhy et al, 2013 ; Klimova and Kozmik, 2014 ). In addition, compound heterozygous and homozygous mutants with other functionally related genes such as Pax2 ( Bäumer et al, 2003 ) and Sox2 ( Matsushima et al, 2011 ) have been analyzed.…”

“…The key initial findings were that Small eye ( Sey ) mouse homozygous model Sey/Sey lacks the eyes ( Hogan et al, 1986 ) and that the causative mutation G194X in the Pax6 coding sequence generates premature stop codon ( Hill et al, 1991 ). However, as Pax6 expression includes all eye tissues, it is unclear how Pax6 mutations cause all these interconnected eye developmental defects as each tissue express Pax6 proteins with variable temporally and spatially regulated intensities and the defects found can be caused by both cell autonomous and non-cell autonomous functions of Pax6 proteins.…”

Multiple roles of Pax6 in corneal limbal epithelial cells and maturing epithelial cell adhesion

“…In cornea, the prevailing PAX6-associated defects are aniridia-associated keratopathy [36, 37] and limbal stem cell deficiency [38]. In contrast, Pax6 homozygous mutations such as Sey/Sey lack the eyes, exhibit major brain, olfactory placode and pancreas abnormalities and die at birth [39].…”