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Generating mouse models of retinal disease using ENU mutagenesis
P N Baird1, R H Guymer, D Chiu
1University of Melbourne, Centre for Eye Research Australia (CERA), University of Melbourne, 32 Gisborne Street, East Melbourne, 3002, Victoria, Australia. pnb@unimelb.edu.au
Vision Research
|February 21, 2002
Summary
Researchers used a chemical mutagen to create mouse models for retinal diseases. This study identified numerous ocular abnormalities, confirming genetic inheritance in several mouse lines with retinal changes.
Area of Science:
- Genetics
- Ophthalmology
- Toxicology
Background:
- Developing genetically modified mouse models is crucial for understanding human diseases.
- Retinal diseases represent a significant cause of vision impairment and blindness worldwide.
- Chemical mutagens offer a method for inducing random genetic mutations to study disease phenotypes.
Purpose of the Study:
- To generate mouse models of retinal diseases using chemical mutagenesis.
- To screen mutagenized mice for ocular abnormalities and identify those with retinal defects.
- To confirm the genetic inheritance of induced ocular and retinal abnormalities.
Main Methods:
- Utilized N-ethyl-N-nitrosourea as a chemical mutagen to induce germline mutations in C57BL/6 mice.
- Examined 1163 first-generation mice for ocular abnormalities.
- Bred 21 mice with ocular abnormalities, including 17 with retinal changes, to subsequent generations to verify inheritance.
Main Results:
- Approximately one-third (412/1163) of the first-generation mice exhibited ocular abnormalities.
- Most abnormalities were unilateral and affected the anterior segment of the eye.
- Less than 10% (44/1163) of abnormalities affected the posterior segment, with 17 mice showing retinal changes. Genetic inheritance was confirmed in several lines, including three with retinal changes.
Conclusions:
- Chemical mutagenesis is an effective method for generating mouse models of ocular and retinal diseases.
- A significant proportion of induced mutations result in ocular abnormalities, with a smaller subset affecting the retina.
- This approach successfully established genetically inherited mouse models for studying retinal diseases.