The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors.
Bottom Line: Topical endoscopic fundal imaging and scanning laser ophthalmoscopy fundus images of all three Crb1(rd8/rd8) lines showed a significant increase in the number of inferior retinal lesions that was strikingly variable between the lines.By whole-genome SNP analysis of the genotype-phenotype correlation, a candidate region on chromosome 15 was identified.This study also provides insight into the nature of the retinal vascular lesions that likely represent a clinical correlate for the formation of retinal telangiectasia or Coats-like vasculopathy in patients with CRB1 mutations that are thought to depend on such genetic modifiers.
Affiliation: Department of Genetics and firstname.lastname@example.org.Show MeSH
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Mentions: To further understand whether the Crb1rd8 allele, possibly by altered expression of the predicted truncated CRB1 protein (16), contributes to the phenotypic variability in different strains and whether expression of Crb2 may be altered in a compensatory way, we quantified Crb1 and Crb2 transcript levels relative to wild type in weakly and severely affected Crb1rd8/rd8 mice (Fig. 3). We also evaluated whether the genetic background of different inbred mouse strains influences the expression level of Crb1 (Supplementary Material, Fig. S1). Crb1 transcripts were significantly reduced to ∼20% of wild type in all Crb1rd8/rd8 mice, independent of the severity of their phenotypes (Fig. 3A). No significant changes in Crb2 transcript levels were observed, although subtle effects cannot be excluded (Fig. 3B). Although Crb1 transcript levels were significantly influenced by different genetic backgrounds, the influence of the homozygous Crb1rd8/rd8 mutation on Crb1 transcript levels was always much more pronounced (Supplementary Material, Fig. S1). Consistent with these data, immunohistochemistry using a C-terminal antibody for Crb1 revealed a weak specific signal across the whole superior and inferior OLM in wild-type retina (OLM; Fig. 3C, white arrow head), but not in any retina from Crb1rd8/rd8 mice (Fig. 3D–F).Figure 3.