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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
Abstract:
We used the chemical mutagen, N-ethyl-N-nitrosourea, to induce random point mutations in the germline of the mouse strain C57BL/6 in order to generate models of retinal diseases. 1163 mutagenised first generation mice produced using this approach were examined for eye abnormalities. Approximately one-third (412) presented with some form of ocular abnormality. Most changes were unilateral and confined to the anterior segment of the eye. Less than 10% (44) of identified changes affected the posterior segment of the eye. 21 mice with varying ocular abnormalities, including 17 with retinal changes, were bred to produce second generation mice to confirm genetic inheritance. Genetic inheritance was confirmed in several of these lines including three with retinal changes.
Insights
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.