Figure 1

The B6 genetic background is permissive to iris phenotypes individually caused by Tyrp1 ^b and Gpnmb ^R150X mutations. (A) The Tyrp1 ^band (B) the Gpnmb ^R150Xcongenic intervals on chromosome 4 and chromosome 6. After 10 generations of backcrossing, the selected D2-derived intervals (filled red box), as well as a limited amount of flanking DNA (empty red box), were present in an essentially B6-derived background (thin blue line). The chromosome 4 interval is delimited proximally by D4Mit214-D4Mit151 and distally by D4Mit185-D4Mit146; the chromosome 6 interval is delimited proximally by D6Mit268-D6Mit207 and distally by D6Mit277-D6Mit16. B6.Tyrp1 ^birides at (C) 4 months, (D) 9 months, and (E) 20 months. From 1–6 months, B6.Tyrp1 ^birides were indistinguishable from wild-type B6. Thereafter, B6.Tyrp1 ^beyes were characterized by a gradual atrophy of iris stromal morphology. Beginning at 6 months, a population of small phagocytic clump cells began to be discernible across the iris surface. With age, the underlying vasculature became obscured, and irides appeared increasingly coarse and atrophic, particularly at the pupil margin where a narrow white band of underlying tissue was exposed. With advanced age, full-thickness iris holes occurred, but rarely before 2 years of age (n = 16 eyes at 1–6 months, 20 eyes at 7–11 months, and 42 eyes at 12+ months). B6.Gpnmb ^R150Xirides at (F) 4 months, (G) 9 months, and (H) 20 months. From 1–5 months, B6.Gpnmb ^R150Xirides were indistinguishable from wild-type B6. Near 6 months, B6.Gpnmb ^R150Xeyes developed a pronounced peripupillary swelling accompanied by pronounced accumulation of clump cells on the iris surface. These swellings remained prominent to the oldest ages examined. The iris surface maintained an overall normal morphology during the first year, after which time it became increasingly atrophic, and accumulations of dispersed pigment were visible on the lens and cornea. No sex-specific differences were evident in the phenotypes of either strain. (n = 16 eyes at 1–6 months, 20 eyes at 7–11 months, and 46 eyes at 12+ months).