The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors.
Bottom Line: This suggests that the Crb1(rd8/rd8) mutation is necessary, but not sufficient for the development of these degenerative features.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 email@example.com.Show MeSH
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Mentions: To establish the degree of phenotypic variability in homozygous Crb1rd8/rd8 mice, we analysed three different Crb1rd8/rd8 mouse lines at 2 months of age using autofluorescent scanning laser ophthalmoscopy (AF-SLO; Fig. 1). All Crb1rd8/rd8 lines showed significantly higher number of autofluorescent lesions in the inferior retina than wild-type mice (Fig. 1). However, a striking variability in the manifestation of this phenotype was observed between lines. While the genetically independent Crb1rd8/rd8/J inbred line showed high and stable number of characteristic large irregular lesions (Fig. 1A–C), significantly fewer lesions were observed in the two closely related lines [Fig. 1M, C57BL/6 Crb1rd8/rd8 (1) and (2)]. Autofluorescent lesions in C57BL/6 Crb1rd8/rd8 (1) mice were small, weak, reduced in number and located more inferiorly (Fig. 1D–F), while typical large lesions were seen in C57BL/6/Crb1rd8/rd8 (2) mice, but with a high degree of variability (Fig. 1G–I and M).Figure 1.