PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Jablonski, M.M.* ; Dalke, C. ; Wang, X.F.* ; Lu, L.* ; Manly, K.F.* ; Pretsch, W. ; Favor, J. ; Pardue, M.T.* ; Rinchik, E.M.* ; Williams, R.W.* ; Goldowitz, D.*

An ENU-induced mutation in Rs1h causes disruption of retinal structure and function.

Mol. Vis. 11, 569-581 (2005)
Verlagsversion Volltext PMC
Free journal
Creative Commons Lizenzvertrag
Purpose: The 44TNJ mutant mouse was generated by the Tennessee Mouse Genome Consortium (TMGC) using an ENU-based mutagenesis screen to produce recessive mutations that affect the eye and brain. Herein we present its retinal phenotype and genetic basis. Methods: Fourth generation offspring (G(4)) and confirmed mutants were examined using slit lamp biomicroscopy, funduscopy, histology, immunohistochemistry, and electroretinography (ERG). 44TNJ mutant mice were crossed to C3BLiA or DBA/2 mice for chromosomal mapping purposes. Linkage analysis by PCR-based microsatellite marker genotyping was used to identify the disease locus. The Rs1h cDNA and its genomic DNA were sequenced directly. Results: The 44TNJ pedigree was the first mutant pedigree identified by the ocular phenotyping domain of the TMGC. Examination of the fundus revealed numerous small and homogeneous intraretinal microflecks in the peripapillary region, which became courser and more irregular in the periphery. Males were typically more affected than females. Histology and immunohistochemistry revealed a disruption of the lamination of the retina, particularly at both margins of the outer nuclear layer, along with reduced calbindin immunostaining. ERG analyses revealed reduced amplitudes of both a-waves and b-waves. Linkage analysis mapped the 44TNJ mutation to the X chromosome close to the marker DXMit117. Sequence analysis of the positional candidate gene Rs1h revealed a T->C exchange at the second base of intron 2 of the Rs1h gene. Conclusions: We have generated and characterized a mutant mouse line that was produced using ENU-based mutagenesis. The 44TNJ pedigree manifests with photoreceptor dysfunction and concurrent structural and functional aberrations at the post-receptoral level. Genetic analysis revealed a mutation in Rs1h, making this the first murine model of X-linked retinoschisis in which the gene is expressed.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Altmetric
2.900
0.000
38
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter X-LINKED RETINOSCHISIS; JUVENILE RETINOSCHISIS; XLRS1 GENE; B-WAVE; BIPOLAR; PROTEIN; CELLS; PHOTORECEPTOR; EXPRESSION; MICE
Sprache englisch
Veröffentlichungsjahr 2005
HGF-Berichtsjahr 0
ISSN (print) / ISBN 1090-0535
e-ISSN 1090-0535
Zeitschrift Molecular Vision
Quellenangaben Band: 11, Heft: 67, Seiten: 569-581 Artikelnummer: , Supplement: ,
Verlag Sun Yat-sen University, P.R. China
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Human Genetics (IHG)
POF Topic(s) 30204 - Cell Programming and Repair
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-002
G-500700-002
PubMed ID 16088326
WOS ID WOS:000231066900001
Erfassungsdatum 2005-08-08
[➜Korrektur melden]