Regional Mutagenesis of the Mouse Genome: An Update of Ocular Phenotypes

Abstract

Abstract: : Purpose: The Tennessee Mouse Genome Consortium (TMGC) is in its second year of a regional ENU-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Chromosomes 7, 10, 14, 15, 16, 19 and X are being targeted. Our goal is to create mutagenized mice that exhibit the phenotypes of human conditions to facilitate finding the cause(s) and cure(s) for various neurological diseases. Herein we present an update of the results of the ocular phenotyping domain of the TMGC. Methods: The TMGC employs a novel mutagenesis program whereby markers (coat color or molecular/PCR-based) identify mice (test class) that potentially carry mutations in specific chromosomal regions. This approach serves as a strong foundation for the genetic dissection of phenotype and genotype relationships by offering an economy of effort and reliability in addition to pre-localizing mutations to discrete regions of the genome. Along with other phenotyping protocols, test class mice are examined by the ocular phenotyping domain (please visit http://tmgc.ornl.gov/neuromutagenesis/index.html for a complete listing of all testing strategies). 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 and lens weights; (4) histological examination of all ocular structures; (5) histo- and immunohistochemical staining of all ocular structures; and (6) ERG testing of retinal function. Results: We have examined 190 pedigrees and approximately 1100 mice at a rate of 12-18 pedigrees per month. We have detected one confirmed and three potential mutant pedigrees, all with a primary retinal defect. Three of the flagged pedigrees have come from the chromosome 15 screen and one from the chromosome 7 screen. We are currently testing heritability of these potential mutations and ruling out involvement of rd1. Additional mice are evaluated each week. Conclusions: We have identified 1 mutant, 2 cutant and 1 putant mice pedigrees through the TMGC mouse mutagenesis project. A detailed analysis of these pedigrees is in progress. Additional mice are undergoing phenotypic evaluation each week. Please contact us if your are interested in collaborating with us to study these or other mutant mice as they become available. You can follow our progress at http://www.tnmouse.org/mutrack.

Keywords: mutations • retina • retinal degenerations: hereditary