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Analysis of mouse eye mutants as models for human diseases
Author(s) -
JADEJA S,
SANGER MGP,
MARY LYON CENTRE MRC,
JACKSON I
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.4145.x
Subject(s) - mutant , knockout mouse , phenotype , biology , microphthalmia , retinal degeneration , mutagenesis , retinal , genetics , pathology , microbiology and biotechnology , gene , medicine , biochemistry
Purpose The Eumodic (European Mouse Disease Clinic) project screens mouse knockout lines and ENU induced mutants for pathological phenotypes. Initially 2 of the strains identified with an eye defect by the Sanger MGP and a strain from the ENU mutagenesis screen at MRC Harwell have been selected for further investigation. Methods Following the initial primary phenotyping, pathology; histology; and immunohistochemistry was carried out on ocular tissue collected from mutant and control animals to determine defects in eye structure and development. This gave an indication to the underlying cause of the defects seen, enabling further molecular biology analysis. Results Btb/Poz Domain‐containing Protein 12 (Btbd12) is a scaffold protein required for the formation of DNA repair complexes. The mouse knockout of this gene shows corneal opacity, dilated pupils and occasional microphthalmia, modelling the phenotypes seen in human diseases of defective DNA repair. The corneas of the mutant animals exhibit increased DNA damage which is likely to be the cause of the opacification. Solute Carrier Family 9 Member 8 (Slc9a8) is a Sodium/ Hydrogen exchanger and has previously been shown to play a role in ion exchange. The Slc9a8 knockout strain appears to have retinal degeneration and the males are infertile. The ENU‐induced mutant Pedv128 exhibits defects in the retinal vasculature including defective vascular patterning and increased vascular leakage. Of particular interest is that this vascular phenotype is restricted to the eyes. Conclusion Investigation of mouse eye mutants can result in a better understanding of the pathology and underlying causes of human diseases.