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The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors.

Luhmann UF, Carvalho LS, Holthaus SM, Cowing JA, Greenaway S, Chu CJ, Herrmann P, Smith AJ, Munro PM, Potter P, Bainbridge JW, Ali RR - Hum. Mol. Genet. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and u.luhmann@ucl.ac.uk.

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Variable manifestation of the inferior retinal degeneration in different Crb1rd8/rd8 mouse lines at 2 months of age. Qualitative and quantitative in vivo phenotyping by AF-SLO of three Crb1rd8/rd8 mouse lines and C57BL/6J Crb1+/+ control mice revealed the variable manifestation of large irregular lesions in the inferior retina. Three representative AF-SLO fundus images for each of the Crb1rd8/rd8 lines are shown (A–C, Crb1rd8/rd8/J; D–F: C57BL/6 Crb1rd8/rd8 (1); G–I: C57BL/6 Crb1rd8/rd8 (2); J–L: C57BL/6J Crb1+/+). M: quantification of the number of lesions per fundus image differed significantly in variance (Bartlett's test for equal variances: P < 0.0001) and in number of lesions between Crb1rd8/rd8 mouse lines. Black lines indicate significant differences with P < 0.0001 using a one-way ANOVA with Tukey's multiple comparison test.
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DDU424F1: Variable manifestation of the inferior retinal degeneration in different Crb1rd8/rd8 mouse lines at 2 months of age. Qualitative and quantitative in vivo phenotyping by AF-SLO of three Crb1rd8/rd8 mouse lines and C57BL/6J Crb1+/+ control mice revealed the variable manifestation of large irregular lesions in the inferior retina. Three representative AF-SLO fundus images for each of the Crb1rd8/rd8 lines are shown (A–C, Crb1rd8/rd8/J; D–F: C57BL/6 Crb1rd8/rd8 (1); G–I: C57BL/6 Crb1rd8/rd8 (2); J–L: C57BL/6J Crb1+/+). M: quantification of the number of lesions per fundus image differed significantly in variance (Bartlett's test for equal variances: P < 0.0001) and in number of lesions between Crb1rd8/rd8 mouse lines. Black lines indicate significant differences with P < 0.0001 using a one-way ANOVA with Tukey's multiple comparison test.

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.


The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors.

Luhmann UF, Carvalho LS, Holthaus SM, Cowing JA, Greenaway S, Chu CJ, Herrmann P, Smith AJ, Munro PM, Potter P, Bainbridge JW, Ali RR - Hum. Mol. Genet. (2014)

Variable manifestation of the inferior retinal degeneration in different Crb1rd8/rd8 mouse lines at 2 months of age. Qualitative and quantitative in vivo phenotyping by AF-SLO of three Crb1rd8/rd8 mouse lines and C57BL/6J Crb1+/+ control mice revealed the variable manifestation of large irregular lesions in the inferior retina. Three representative AF-SLO fundus images for each of the Crb1rd8/rd8 lines are shown (A–C, Crb1rd8/rd8/J; D–F: C57BL/6 Crb1rd8/rd8 (1); G–I: C57BL/6 Crb1rd8/rd8 (2); J–L: C57BL/6J Crb1+/+). M: quantification of the number of lesions per fundus image differed significantly in variance (Bartlett's test for equal variances: P < 0.0001) and in number of lesions between Crb1rd8/rd8 mouse lines. Black lines indicate significant differences with P < 0.0001 using a one-way ANOVA with Tukey's multiple comparison test.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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DDU424F1: Variable manifestation of the inferior retinal degeneration in different Crb1rd8/rd8 mouse lines at 2 months of age. Qualitative and quantitative in vivo phenotyping by AF-SLO of three Crb1rd8/rd8 mouse lines and C57BL/6J Crb1+/+ control mice revealed the variable manifestation of large irregular lesions in the inferior retina. Three representative AF-SLO fundus images for each of the Crb1rd8/rd8 lines are shown (A–C, Crb1rd8/rd8/J; D–F: C57BL/6 Crb1rd8/rd8 (1); G–I: C57BL/6 Crb1rd8/rd8 (2); J–L: C57BL/6J Crb1+/+). M: quantification of the number of lesions per fundus image differed significantly in variance (Bartlett's test for equal variances: P < 0.0001) and in number of lesions between Crb1rd8/rd8 mouse lines. Black lines indicate significant differences with P < 0.0001 using a one-way ANOVA with Tukey's multiple comparison test.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and u.luhmann@ucl.ac.uk.

Show MeSH
Related in: MedlinePlus