title: Loss of retinoschisin (RS1) cell surface protein in maturing mouse rod photoreceptors elevates the luminance threshold for light-driven translocation of transducin but not arrestin.
abstract: Loss of retinoschisin (RS1) in Rs1 knock-out (Rs1-KO) retina produces a post-photoreceptor phenotype similar to X-linked retinoschisis in young males. However, Rs1 is expressed strongly in photoreceptors, and Rs1-KO mice have early reduction in the electroretinogram a-wave. We examined light-activated transducin and arrestin translocation in young Rs1-KO mice as a marker for functional abnormalities in maturing rod photoreceptors. We found a progressive reduction in luminance threshold for transducin translocation in wild-type (WT) retinas between postnatal days P18 and P60. At P21, the threshold in Rs1-KO retinas was 10-fold higher than WT, but it decreased to <2.5-fold higher by P60. Light-activated arrestin translocation and re-translocation of transducin in the dark were not affected. Rs1-KO rod outer segment (ROS) length was significantly shorter than WT at P21 but was comparable with WT at P60. These findings suggested a delay in the structural and functional maturation of Rs1-KO ROS. Consistent with this, transcription factors CRX and NRL, which are fundamental to maturation of rod protein expression, were reduced in ROS of Rs1-KO mice at P21 but not at P60. Expression of transducin was 15-30% lower in P21 Rs1-KO ROS and transducin GTPase hydrolysis was nearly twofold faster, reflecting a 1.7- to 2.5-fold increase in RGS9 (regulator of G-protein signaling) level. Transduction protein expression and activity levels were similar to WT at P60. Transducin translocation threshold elevation indicates photoreceptor functional abnormalities in young Rs1-KO mice. Rapid reduction in threshold coupled with age-related changes in transduction protein levels and transcription factor expression are consistent with delayed maturation of Rs1-KO photoreceptors.
authors.affiliation: G B Bietti Foundation, Istituto di Ricovero e Cura a Carattere Scientifico, 00198 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ziccardi
authors.forename: Camasamudram
authors.initials: C
authors.lastname: Vijayasarathy
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Bush
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019393:Arrestin / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000172:deficiency*; D003623:Dark Adaptation / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D004596:Electroretinography; D005136:Eye Proteins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D055537:Light Signal Transduction / Q000235:genetics*; D049449:Luminescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010775:Photic Stimulation; D017785:Photons; D017440:Photoperiod; D021381:Protein Transport / Q000235:genetics; D012160:Retina / Q000166:cytology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors; D015293:Transducin / Q000378:metabolism*; D014795:Visual Pathways / Q000502:physiology
chemical_list: D019393:Arrestin; D015815:Cell Adhesion Molecules; D005136:Eye Proteins; C491843:RS1 protein, mouse; D012243:Rhodopsin; D020558:GTP Phosphohydrolases; D015293:Transducin