Research Report Modifications of the retina neuronal populations of the heterozygous mutant small eye mouse, the Sey Dey Gloria González Curto, Juan Manuel Lara, Marta Parrilla, José Aijón, Almudena Velasco ⁎ Instituto de Neurociencias de Castilla y León, Departamento de Biología Celular, Universidad de Salamanca, 37007 Salamanca, Spain ARTICLE INFO ABSTRACT Article history: Accepted 3 October 2006 Available online 17 November 2006 We analyzed the modifications of the retinal neurons in a heterozygous mutant small eye mouse, the Sey Dey . This mouse presents a mutation in chromosome 2 which affects the gene Pax6 and other nearby genes, such as the Wt1 gene and the gene of the Reticulocalbin. The eyes of these animals do not have lenses and their retinas present important morphological alterations: in the anterior portion they are joined to the cornea, they are found detached from the pigment epithelium, they present folds that form rosettes in some zones and alteration of the lamination can be observed. The partial loss of the genes affected does not prevent the formation of the different layers of the retina, but does affect its thickness, principally of the plexiform layers; moreover, the internal limiting membrane is found disorganized. All the neuronal populations are present in the retina of these animals and express the same neurochemical markers as the control animals, but the number of Pax6 + cells is notably reduced. In these retinas a marked disorganization of the distribution of the dendrites and axons is observed and a notable reduction in the axons of ganglion cells. These results suggest that, although it does not appear determinant in the differentiation of the distinct neuronal types of the retina, the partial lack of genes of the heterozygotes +/Sey Dey provokes important morphological and neurochemical modifications in the cytoarchitecture of the retina. © 2006 Elsevier B.V. All rights reserved. Keywords: Pax6 Wt1 Reticulocalbin Retina Mutant mouse Haploinsufficiency 1. Introduction The Sey Dey mouse has an autosomic mutation, semi-dominant and of high penetrance denominated Dickie's small eye (Theiler et al., 1978, 1980). The mutation in Sey Dey consists of a deletion localized in chromosome 2 which extends between 1370 and 2300 kb, eliminating all or part of the gene Pax6, of the gene of the tumor of Wilms of the mouse (Wt1) and of the gene of the reticulocalbin (Rcn)(Glaser et al., 1990; Kent et al., 1997). The homozygotes ( Sey Dey /Sey Dey ) die before the sixth day of gestation (E6). The heterozygotes (+/Sey Dey ) are viable, they have a variable phenotype, but are identified by the reduced size of the eyes and by the lack of protuberance of the ocular globe (Theiler et al., 1978). The eyelids can be closed or present a small aperture through which cataracts can be observed (Theiler et al., 1978, 1980). Furthermore, the animals affected present a reduction in body size of approximately 10% with respect to the control animals (Theiler et al., 1978). From E12, the most evident characteristic of the Sey Dey heterozygotes is their ocular abnormality. The lens appears 1 or 2 days after those of the control animals and the lens does not separate from the cornea. In perinatal stages the eye is BRAIN RESEARCH 1127 (2007) 163 – 176 ⁎ Corresponding author. Biología Celular, INCyL, Facultad de Medicina, Campus Unamuno, 37007 Salamanca, Spain. Fax: +34 923294549. E-mail address: malmu@usal.es (A. Velasco). 0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.10.007 available at www.sciencedirect.com www.elsevier.com/locate/brainres