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Novel phenotypes identified by plasma biochemical screening in the mouse
Tertius A Hough1, Patrick M Nolan, Vicky Tsipouri
1MRC Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, OX11 ORD, UK. tertius@har.mrc.ac.uk
Summary
ENU mutagenesis rapidly generated novel mouse models with metabolic phenotypes. A validated blood biochemistry screen identified inherited abnormalities in lipids, bone, liver, electrolytes, and glucose, aiding gene function and disease studies.
Area of Science:
- Genetics and Genomics
- Animal Models
- Biochemistry
Background:
- Mouse models are crucial for gene function studies and modeling human diseases.
- Chemical mutagenesis, such as N-ethyl-N-nitrosourea (ENU) mutagenesis, is a powerful tool for generating genetic variation.
- Developing efficient screening methods is essential for identifying novel mutant phenotypes.
Purpose of the Study:
- To rapidly generate novel mutant mouse phenotypes using ENU mutagenesis.
- To develop and validate a high-throughput blood biochemistry screen for identifying metabolic abnormalities.
- To create new animal models for studying gene function and human diseases.
Main Methods:
- Utilized ENU mutagenesis in mice to induce genetic mutations.
- Collected blood from F1 offspring and performed a 17-test plasma biochemistry profile.
- Screened 1,961 F1 mice, identifying outliers and performing inheritance testing on 29 mice with consistent abnormalities.
Main Results:
- Identified 9 inherited metabolic phenotypes from 29 tested.
- Confirmed abnormalities in lipid profiles, bone and liver metabolism (ALP, ALT, AST), plasma electrolytes (sodium, chloride), and glucose levels.
- Validated the blood biochemistry screen's effectiveness for identifying diverse metabolic mutations.
Conclusions:
- The ENU mutagenesis and biochemical screening approach successfully generated novel mouse mutants with defined metabolic phenotypes.
- The validated screen is applicable to other mutagenesis projects for identifying genetic variations.
- These new models offer valuable resources for studying gene function and human metabolic diseases.