Physiological function of S-cone system is not enhanced in rd7 mice Shinji Ueno a , Mineo Kondo a, * , Kentaro Miyata a , Toshie Hirai a , Takaki Miyata b , Jiro Usukura b , Yuji Nishizawa b , Yozo Miyake a a Department of Ophthalmology, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan b Department of Anatomy and Cell Biology, Nagoya University School of Medicine, Nagoya 466-8550, Japan Received 2 October 2004; accepted in revised form 23 April 2005 Available online 11 July 2005 Abstract The rd7mouse is a mutant mouse with a relatively late development of retinal degeneration. Earlier studies have shown that rd7 mice have a distinctive pattern of retinal dysplasia with an increased number of cone cells, particularly those with S (short wavelength)-opsin immunoreactivity. These alterations of the rd7 retina are caused by a mutation in the photoreceptor cell-specific nuclear receptor gene, Nr2e3, which is involved in the signaling pathway regulating photoreceptor cell differentiation, cell maintenance, and cell–cell interactions. The purpose of this study was to determine the physiological properties of the rd7 retina using electroretinographic (ERG) techniques. We found that the maximal a-wave amplitude of the ERG in rd7 mice was already reduced to half of the congenic controls at 6 weeks of age with normal phototransduction sensitivity. The photopic ERGs of rd7 mice were not supernormal, and the amplitudes of the S-cone ERGs were not significantly different from those recorded in controls. These results suggested that even though the number of cones expressing S-opsin is increased, the physiological function of the S-cone system is not enhanced in rd7 mice. q 2005 Elsevier Ltd. All rights reserved. Keywords: electroretinogram; mouse; Nr2e3; rd7; retinal degeneration 1. Introduction The rd7 mouse is a mutant mouse with an autosomal recessive retinal degeneration (Chang et al., 1998; Akhmedov et al., 2000). There is a progressive degeneration of both the rod and cone systems, and ophthalmoscopy showed multiple white spots across the entire retina (Akhmedov et al., 2000). Histological examination demon- strated a distinctive pattern of dysplasia with waves, whorls, and rosettes in the outer nuclear layer (Chang et al., 1998; Akhmedov et al., 2000; Haider et al., 2001). Immunocyto- chemical studies showed that there was an increased number of cones, especially S (short-wavelength)-opsin expressing cone cells in the retina of rd7 mice (Haider et al., 2001). These alterations of the retina resulted from a deletion of the photoreceptor cell specific nuclear receptor gene, Nr2e3 (Akhmedov et al., 2000; Haider et al., 2001), which is known to be involved in the signaling pathway regulating photoreceptor cell differentiation, cell maintenance, and cell–cell interactions (Kobayashi et al., 1999; Haider et al., 2001; Yanagi et al., 2002). In humans, mutations of the same Nr2e3 gene were identified in patients with a unique type of retinal dystrophy called the enhanced S-cone syndrome (ESCS) (Haider et al., 2000). ESCS is an autosomal recessive retinal disorder which is characterized by night blindness, and an abnormally increased amplitude of the S-cone ERG (Marmor et al., 1990; Jacobson et al., 1990). Analysis of the electroretinograms (ERGs) in ESCS patients led to the hypothesis that there were more S-cones in the retina of these patients than in normals (Hood et al., 1995). Using imunocytochemical techniques on a postmortem retina, Milam et al. (2002) demonstrated that the number of cones was actually increased by approximately 2-fold, and 92% of these were S-cones. Thus, Nr2e3 appeared to play an important role in the signaling pathway that controls the development and differentiation of this type of photo- receptor in both mice and humans. The purpose of this study was to determine if these morphological alterations affected the physiological Experimental Eye Research 81 (2005) 751–758 www.elsevier.com/locate/yexer 0014-4835/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.exer.2005.04.013 * Corresponding author. E-mail address: kondomi@med.nagoya-u.ac.jp (M. Kondo).