Mouse Genome Informatics
cx
    Abca4tm1Ght/Abca4tm1Ght
Rdh8tm1Kpal/Rdh8tm1Kpal

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
vision/eye
• Choroidal Neovascularization (CNV) in 22.2% (2/9) of the eyes
• no Choroidal Neovascularization (CNV) in the eyes of sirolimus-treated mice
• reduced number of photoreceptor nuclei along the inferior retinal regions and severe retinal degeneration at 5 months and 10 months of age, respectively
• reduced number of cone photoreceptors
• retinylamine treatment largely preserve cone photoreceptors
• antioxidant, 9cRAc, and sirolimus treatment preserve cone photoreceptors, but not as well as retinylamine
• swollen retinal pigment epithelium (RPE) with increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age
• disrupted inner membrane cristae in RPE cells at 5 months of age
• dead RPE cells lacking mitochondrial inner membrane cristae at 10 months of age
• increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age
• di-retinoidpyridinium-ethanolamine (A2E) accumulation
• retinylamine significantly decreased A2E accumulation
• severely reduced outer nuclear layer
• early retinal degeneration is detected by 6 to 8 weeks of age in mice kept in dim room light (3-5 lux)
• reduced lengths of photoreceptor outer segments (less than 5 micrometers)
• antioxidant, 9cRAc, retinylamine and sirolimus treatment have efficacy in preventing retinal degeneration
• hyaline-like deposits in the rosette structure in 3- to 5-month-old mutant mice
• complement deposition on Bruch's membrane
• reduced complement deposition in antioxidant, 9cRAc, and sirolimus-treated mice
• no complement deposition in retinylamine-treated mice
• reduced a- and b-wave amplitudes
• both a- and b-wave amplitudes are maintained significantly better in antioxidant, 9cRAc, retinylamine and sirolimus-treated mice
• reduced Flicker ERG responses
• responses of some antioxidant- and 9cRAc-treated mice are significantly retained after both 20- and 30-Hz stimuli

nervous system
• reduced number of photoreceptor nuclei along the inferior retinal regions and severe retinal degeneration at 5 months and 10 months of age, respectively
• reduced number of cone photoreceptors
• retinylamine treatment largely preserve cone photoreceptors
• antioxidant, 9cRAc, and sirolimus treatment preserve cone photoreceptors, but not as well as retinylamine

pigmentation
• swollen retinal pigment epithelium (RPE) with increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age
• disrupted inner membrane cristae in RPE cells at 5 months of age
• dead RPE cells lacking mitochondrial inner membrane cristae at 10 months of age
• increased pigmented granules that included lipofuscin in mice kept in room light at 5 months of age
• di-retinoidpyridinium-ethanolamine (A2E) accumulation
• retinylamine significantly decreased A2E accumulation

cardiovascular system
• Choroidal Neovascularization (CNV) in 22.2% (2/9) of the eyes
• no Choroidal Neovascularization (CNV) in the eyes of sirolimus-treated mice

Mouse Models of Human Disease
OMIM IDRef(s)
Macular Degeneration, Age-Related, 2; ARMD2 153800 J:154536