CHARACTERIZATION OF GENE/GENE INTERACTIONS INVOLVING Crb1rd8.

Abstract

Abstract: : Purpose: To determine the basis for the genetic interactions between Crb1^rd8 and the CAST/EiJ genetic background (Experiment 1) and Crb1^rd8 and Mfrp^rd6 (Experiment 2 ). Methods: F1 progeny from a B6.Cg–Crb1^rd8J (n3) and CAST/EiJ mating were intercrossed. Mice were genotyped with SSLP markers flanking the rd8 mutation and phenotyped by indirect ophthalmoscopy for retinal spotting in the inferior nasal quadrant at 8 weeks of age. B6.Cg–Crb1^rd8J (n5) and B6.C3Ga–Mfrp^rd6J (n10) were intercrossed and genotyped. Mice that were homozygous for both mutations were examined clinically by indirect ophthamoscopy and histologically. Results: Experiment 1 – Nineteen percent of mice that were genotypically rd8/rd8 in the F2 intercross between B6.Cg–Crb1^rd8J (n3) and CAST/EiJ were suppressed for the retinal spotting phenotype. The suppression was able to rescue the shortening and disorganization of the PR inner and outer segments observed in B6.Cg–Crb1^rd8J (n5) and reduces fragmentation of the ELM. Experiment 2 – Originally, in a mixed C3HfB/GaCas1b and B6 genetic background, rd6 and rd8 were interacting in vivo to cause a more severe phenotype than either allele alone. Large spots were observed across the fundus. After making both mutations congenic on B6 by consecutive backcrossing, this interaction was not observed in compound homozygous animals. Conclusions: The CAST/EiJ genetic background is able to suppress the retinal spotting phenotype in B6.Cg–Crb1^rd8J (n3) mice. This suppression corresponds to a rescue of the dysplastic phenotype but does not eliminate the fragmentation of the ELM. Genetic factors from C3HfB/GaCas1b are necessary for the phenotypic interaction, of earlier onset and more severe disease, between rd6 and rd8.

Keywords: retinal degenerations: hereditary • genetics • cell adhesions/cell junctions