Abstract
Abstract: :
Purpose:We have generated and characterized a novel mutant mouse model with an aberrant phenotype primarily affecting the outer retina. This mouse was generated by the Tennessee Mouse Genome Consortium (TMGC) using a regional ENU–based mutagenesis screen to produce recessive mutations that affect the eye and brain. Herein we present a mutant mouse model with a novel retinal phenotype primarily affecting photoreceptor to secondary neuron processing. Methods: Test class mice (G4) were examined by the ocular phenotyping domain of the TMGC. Our screening protocol exploits the following techniques: (1) slit lamp biomicroscopic examination of the anterior segment; (2) fundus examination using the Kowa Genesis ophthalmoscope; (3) measurement of eye weights; (4) histological examination of all ocular structures; (5) histo– and immunohistochemical staining of all ocular structures; and (6) ERG testing of retinal function. To be classified as a mutant mouse pedigree, an aberrant phenotype must be confirmed in a minimum of three independent groups of mice from a minimum of two generations. 44TNJ (tmgc1) mutant mice were crossed to C3BliA for chromosomal mapping purposes. Results: The 44TNJ (tmgc1) pedigree was the first mutant pedigree identified by the ocular phenotyping domain of the TMGC. The slit lamp examination of all 44TNJ mice was unremarkable and the eye weights were within normal limits when compared to other pedigrees of identical background strains. Examination of the fundus revealed numerous intraretinal microflecks that are small and homogeneous around the optic nerve head, which became courser and more irregular in the periphery. Males were typically more affected than females. Histology and immunohistochemistry revealed a disruption of the lamination of the retina, particularly at both margins of the outer nuclear layer along with reduced calbindin immunostaining. ERG analysis revealed reductions in both a– and b– waves and a delayed recovery after a bright flash. Mapping indicated linkage to Chr X. Conclusions: We have generated and characterized a novel mutant mouse line that was produced using an ENU–mutagenesis strategy. The 44TNJ (tmgc1) pedigree manifests with photoreceptor dysfunction and a concurrent problem at the post–receptoral level. We hypothesize that the mutant gene(s) responsible for this phenotype are likely involved in interactions between photoreceptors and second–order retinal neurons.
Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • mutations • photoreceptors