A CNS-Specific Hypomorphic Pdgfr-Beta Mutant Model of Diabetic Retinopathy

Shalini Jadeja, Richard L Mort, Margaret Keighren, Alan W Hart, Russell Joynson, Sara Wells, Paul K Potter, Ian J Jackson

Research output: Contribution to journalArticlepeer-review


PURPOSE: A mouse mutant identified during a recessive ENU mutagenesis screen exhibited ocular haemorrhaging resulting in a blood filled orbit, and hence was named 'redeye'. We aimed to identify the causal mutation in redeye, and evaluate it as a model for Diabetic Retinopathy (DR). METHODS: The causative gene mutation in redeye was identified by haplotype mapping followed by exome sequencing. Glucose tolerance tests, detailed histological and immunofluorescence analyses, and vascular permeability assays were performed to determine the affect of redeye on glucose metabolism, pericyte recruitment and the development of the retinal vasculature and the blood retinal barrier (BRB). RESULTS: A mutation was identified in the Pdgfrb gene at position +2 of intron 6. We show that this change causes partial loss of normal splicing resulting in a frameshift and premature termination, and therefore a substantial reduction in normal Pdgfrb transcript. The animals exhibit defective pericyte recruitment restricted to the central nervous system (CNS) causing basement membrane and vascular patterning defects, impaired vascular permeability and aberrant BRB development, resulting in vascular leakage and retinal ganglion cell apoptosis. Despite exhibiting classical features of diabetic retinopathy redeye glucose tolerance is normal. CONCLUSIONS: The Pdgfrb(redeye/redeye) mice exhibit all of the features of non-proliferative DR including retinal neurodegeneration. In addition, the perinatal onset of the CNS-specific vascular phenotype negates the need to age animals or manage diabetic complications in other organs. Therefore they are a more useful model for diseases involving pericyte deficiencies such as DR than those currently being used.
Original languageEnglish
Pages (from-to)3569-3578
Journal Investigative Ophthalmology & Visual Science (IOVS)
Issue number5
Publication statusPublished - 30 Apr 2013


  • PdgfrB
  • mouse model
  • Diabetic retinopathy


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