title: Cone versus rod disease in a mutant Rpgr mouse caused by different genetic backgrounds.
abstract: OBJECTIVE
  To establish mouse models for RPGR-associated diseases by generating and characterizing an Rpgr mutation (in-frame deletion of exon 4) in two different genetic backgrounds (BL/6 and BALB/c).
  
  
  METHODS
  Gene targeting in embryonic stem (ES) cells was performed to introduce a in-frame deletion of exon 4 in the Rpgr gene (Rpgr(DeltaEx4)). Subsequently, the mutation was introduced in two different inbred mouse strains by successive breeding. Mutant and wild-type mice of both strains were characterized by electroretinography (ERG) and histology at five time points (1, 3, 6, 9, and 12 months). RPGR transcript amounts were assessed by quantitative RT-PCR. A variety of photoreceptor proteins, including RPGR-ORF15, RPGRIP, PDE6delta/PrBPdelta, rhodopsin, and cone opsin, were localized on retinal sections by immunohistochemistry.
  
  
  RESULTS
  Mislocalization of rhodopsin and cone opsin was an early pathologic event in mutant mice of both lines. In contrast, RPGR-ORF15 as well as RPGRIP1 and PDE6delta/PrBPdelta showed similar localizations in mutant and wild-type animals. Functional and histologic studies revealed a mild rod-dominated phenotype in mutant male mice on the BL/6 background, whereas a cone-dominated phenotype was observed for the same mutation in the BALB/c background.
  
  
  CONCLUSIONS
  Both Rpgr mutant mouse lines developed retinal disease with a striking effect of the genetic background. Cone-specific modifiers might influence the retinal phenotype in the BALB/c strain. The two lines provide models to study RPGR function in rods and cones, respectively.
authors.affiliation: Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brunner
authors.forename: Sergej
authors.initials: S
authors.lastname: Skosyrski
authors.forename: Renate
authors.initials: R
authors.lastname: Kirschner-Schwabe
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Knobeloch
authors.forename: John
authors.initials: J
authors.lastname: Neidhardt
authors.forename: Silke
authors.initials: S
authors.lastname: Feil
authors.forename: Esther
authors.initials: E
authors.lastname: Glaus
authors.forename: Ulrich F O
authors.initials: UF
authors.lastname: Luhmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Rüther
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Berger
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D004596:Electroretinography; D053595:Embryonic Stem Cells / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D055355:Opsins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000502:physiology; D012164:Retinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D055355:Opsins; D011506:Proteins; C513598:RPGR protein, mouse; C540216:Rpgrip1 protein, mouse; D012243:Rhodopsin; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6