title: The severity of retinal degeneration in Rp1h gene-targeted mice is dependent on genetic background.
abstract: OBJECTIVE
  The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1h(tm1Eap)) on several different genetic backgrounds and analyzed their retinal phenotypes.
  
  
  METHODS
  The Rp1h(tm1Eap) allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy.
  
  
  RESULTS
  Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h(+/tm1Eap), DBA.129S(B6)-Rp1h(+/tm1Eap), and A.129S(B6)-Rp1h(+/tm1Eap) mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h(+/tm1Eap) mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h(+/tm1Eap) mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h(+/tm1Eap) mice remain healthy up to 18 months.
  
  
  CONCLUSIONS
  The severity of the retinal degeneration caused by the Rp1h(tm1Eap) allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h(+/tm1Eap) and A.129S(B6)-Rp1h(+/tm1Eap) congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease.
authors.affiliation: F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Alexei
authors.initials: A
authors.lastname: Saveliev
authors.forename: Eric A
authors.initials: EA
authors.lastname: Pierce
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004596:Electroretinography; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D007091:Image Processing, Computer-Assisted; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D008869:Microtubule-Associated Proteins; C497821:RP1 protein, mouse