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 better understand how the loss of the evenly distributed CRB1 protein at the OLM might lead to a preferential degeneration in the inferior retina and to see whether all Crb1rd8/rd8 homozygous mice are similarly affected, we evaluated the integrity of the OLM in the three differentially affected Crb1rd8/rd8 lines (Fig. 4). Confocal evaluation on semithin sections across the whole retina suggested that the OLM of C57BL/6 Crb1rd8/rd8 (1) mice is macroscopically similar to that of wild-type mice (white arrow heads; Fig. 4D versus E and I versus J). Also the tight junction protein ZO-1 is evenly distributed along the whole OLM in all Crb1rd8/rd8 and wild-type mice (Fig. 4K–O and Ki–Oi). ZO-1 labelling only became disrupted in the inferior retina if photoreceptor columns were disorganized (red arrow heads, Fig. 4F–J), photoreceptor nuclei dropped out of the ONL (red arrow heads, Fig. 4F–J) and localized Müller glia became activated (Fig. 4K–M). All these features were barely detectable in C57BL/6 Crb1rd8/rd8 (1) mice (Fig. 4N and Ni, red arrowhead) and difficult to distinguish from observations in wild-type mice (Fig. 4E and J and O and Oi).Figure 4.