Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure

Weber, Bernhard H. F.; Schrewe, Heinrich; Molday, Laurie L.; Gehrig, Andrea; White, Karen L.; Seeliger, Mathias W.; Jaissle, Gesine B.; Friedburg, Christoph; Tamm, Ernst R.; Molday, Robert S.

doi:10.1073/pnas.092528599

Cited by 188 publications

(204 citation statements)

References 31 publications

(30 reference statements)

Supporting

Mentioning

191

Contrasting

Unclassified

Order By: Relevance

“…16 All three XLRS1h knockout models displayed morphological and functional retinal phenotypes similar to human XLRS. Fundus examination revealed the presence of small cyst-like structures in the inner retina of the XLRS1h 2/Y mouse 14 and intraretinal flecks in 44TNJ mouse. 16 Similarly, ERG analysis of all three mouse models showed a characteristic reduced darkadapted b-wave.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Histologically, the mice displayed disorganisation of retinal layers due to mislocalisation of cells within the inner plexiform, inner nuclear and outer plexiform layers; focal areas of retinal splitting or ''schisis'' were also evident within the inner nuclear layer and structural abnormalities of synapses occur within the outer plexiform layer. [14][15][16] …”

Section: Animal Modelsmentioning

confidence: 99%

“…[10][11][12][13] Three retinoschisis mouse models have been developed and they have similar retinal pathology to the human disease. [14][15][16] This article aims to review the clinical, pathological and electrophysiological features of XLRS, our current understanding of its molecular basis and to consider future therapy.…”

mentioning

confidence: 99%

See 2 more Smart Citations

X-linked retinoschisis: an update

Sikkink

Biswas

Parry

et al. 2007

Journal of Medical Genetics

145

127

View full text Add to dashboard Cite

Section: Animal Modelsmentioning

confidence: 99%

Section: Animal Modelsmentioning

confidence: 99%

See 1 more Smart Citation

X-linked retinoschisis: an update

Sikkink

Biswas

Parry

et al. 2007

Journal of Medical Genetics

145

127

View full text Add to dashboard Cite

“…(4) Esse gene codifica uma proteína composta por 224 aminoácidos, a retinosquisina, sintetizada no segmento interno dos fotorreceptores. Essa proteína proporciona adesão entre as células retinianas, interação entre as células da camada nuclear interna, bem como conexão sináptica entre fotorreceptores e células bipolares, mantendo a estrutura retiniana (5,6) . Na retinosquise juvenil, a disfunção da retinosquisina leva ao seu acúmulo nas camadas retinianas internas (7)(8)(9) , com consequente formação de espaços císticos nas camadas nuclear interna e plexiforme externa observados na tomografia de coerência óptica (OCT) (10,11) .…”

Section: Introductionunclassified

Uso da dorzolamida tópica em paciente portador de retinosquise juvenil ligada ao X

Caye¹,

Barbosa

Scheid³

et al. 2010

Rev. bras.oftalmol.

View full text Add to dashboard Cite

RESUMOA retinosquise juvenil ligada ao cromossomo X é uma degeneração vítreorretiniana hereditária e recessiva. Sua manifestação ocular é a maculopatia cística bilateral e a delaminação das camadas de fibras nervosas da retina. Nenhuma intervenção terapêu-tica se mostrou eficiente para estabilizar a acuidade visual nestes pacientes. O artigo relata o caso clínico de um paciente portador de retinosquise juvenil ligada ao cromossomo X, que foi tratado com o uso tópico da dorzolamida, um colírio inibidor da anidrase carbônica.

show abstract

“…Retina; Retinoschisin; Post-Translational Modifications; Isoforms; Signal Sequence; Signal peptidase; Processing; X-linked retinoschisis; Missense mutations Retinoschisin (RS) is a 24 kDa secreted protein expressed in retina and pineal * and is required for the structural and functional integrity of the retina [1]. Based on its conserved discoidin domain sequence, RS is predicted to serve as an adhesion protein in maintaining the organization of the retina [1] but a precise molecular description of RS function is not yet known.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of two mature isoforms of retinoschisin in murine retina

Vijayasarathy

Gawinowicz

Zeng

et al. 2006

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Retinoschisin (RS) is a 24 kDa secreted protein expressed in retina and is required for the structural and functional integrity of the retina. RS has been predicted to serve as an adhesive protein but the precise molecular mechanism by which it functions in retina is not yet known. During investigations on structural and functional aspects of RS in murine retina using proteomic tools, we identified two isoforms of RS that differed in mass by 200 Da with no apparent change in charge. Mass spectra and amino acid sequence analysis of the tryptic peptides revealed that these isoforms differed by two amino acids at the N-terminus which suggested processing of RS signal sequence at two cleavage sites by signal peptidase as the basic mechanism underlying the occurrence of two mature RS isoforms in retina. Bioinformatic analysis identified two potential cleavage sites (between amino acids 21-22 and 23-24) in RS signal sequence. The flexibility of the signal peptidase to cleave at two sites is correlated to the amino acid composition of the RS signal sequence. This finding represents a rare example of a naturally occurring signal sequence cleavage at more than one site in vivo. KeywordsRetina; Retinoschisin; Post-Translational Modifications; Isoforms; Signal Sequence; Signal peptidase; Processing; X-linked retinoschisis; Missense mutations Retinoschisin (RS) is a 24 kDa secreted protein expressed in retina and pineal * and is required for the structural and functional integrity of the retina [1]. Based on its conserved discoidin domain sequence, RS is predicted to serve as an adhesion protein in maintaining the organization of the retina [1] but a precise molecular description of RS function is not yet known. Mutations in the RS1 gene that encodes the RS protein cause monogenic X-linked retinoschisis (XLRS) in young males [2][3][4]. Retinoschisis is a form of juvenile macular Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. * Takada et. al.(2006 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript degeneration in which schisis or splitting within the nuclear and plexiform layers of the retina [5] leads to progressive loss of vision beginning at a young age [6]. Gene therapy is being considered as a therapeutic approach to treat XLRS disease which otherwise has no known cure [7].RS is synthesized in retinal photoreceptor, bipolar amacrine and ganglion cells [8,9]. The 224 amino acid RS polypeptide consists of a 23 amino acid leader sequence followed by a 39 amino acid RS domain, a highly conserved 157 amino acid discoidin domain and a 5 amino acid Ctermin...

show abstract

Inactivation of the murine X-linked juvenile retinoschisis gene, Rs1h, suggests a role of retinoschisin in retinal cell layer organization and synaptic structure

Cited by 188 publications

References 31 publications

X-linked retinoschisis: an update

X-linked retinoschisis: an update

Uso da dorzolamida tópica em paciente portador de retinosquise juvenil ligada ao X

Identification and characterization of two mature isoforms of retinoschisin in murine retina

Contact Info

Product

Resources

About