Mitochondrial-Nuclear Exchanged Animals for Disease Modeling
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Solution Overview
Problem
Current methods are inadequate for understanding and modeling the interaction between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) in determining disease susceptibility and resistance, particularly for conditions like cardiovascular disease, cancer, and diabetes, due to the complexity of examining mitochondrial function and interactions in human populations.
Innovation Solution
The creation of mitochondrial-nuclear exchanged animals, where the mtDNA from one strain is combined with the nDNA from another, allowing for the study of how mitochondrial-nuclear interactions influence disease susceptibility and resistance, using techniques such as nuclear transfer and genotyping to confirm genetic identities and assess mitochondrial function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mitochondrial-nuclear exchanged animals are created to study disease susceptibility, then the ability to determine mechanistic and genetic basis of disease is improved, but the complexity of the experimental model increases
Solution Approach 1:
The invention segments the genetic material into two separate components: mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). By creating animals with exchanged mitochondrial-nuclear genomes, the patent isolates the effects of mitochondrial genetics from nuclear genetics, allowing independent study of each component's contribution to disease susceptibility. This segmentation enables precise determination of mechanistic and genetic bases without the confounding complexity of studying both genomes simultaneously in their natural coupled state.
2Ease of manufacture
If nuclear transfer technique is used to create mitochondrial-nuclear exchanged animals, then the ability to control genetic composition is improved, but the difficulty of the procedure increases
Solution Approach 1:
The invention extracts the nucleus from donor cells and transfers it into enucleated recipient eggs. This extraction and transfer process allows precise control over the genetic composition of the resulting animals, as researchers can select specific nuclear and mitochondrial DNA combinations. The nuclear transfer technique enables the separation and recombination of genetic materials in a controlled manner, achieving the desired genetic composition despite the procedural complexity involved in enucleation and nuclear injection.
3Loss of information
If mitochondrial-nuclear exchanged animals are used for disease modeling, then the understanding of mitochondrial-nuclear interactions is improved, but the time required to generate and validate models increases
Solution Approach 1:
The invention performs preliminary genetic manipulation by creating mitochondrial-nuclear exchanged animals with predetermined genetic compositions before disease development occurs. By establishing the desired mitochondrial-nuclear combinations in advance, researchers can directly study the interactions between these genetic components in the context of specific diseases without the need for lengthy breeding programs or complex cross-breeding schemes. This preliminary action significantly reduces the time required to generate valid disease models while maximizing the understanding of mitochondrial-nuclear interactions.
Data Source
AI summary
Provided herein are mitochondrial-nuclear exchanged cells and animals comprising mitochondrial DNA (mtDNA) from one subject and nuclear DNA (nDNA) from a different subject. Methods for producing a mitochondrial-nuclear exchanged animal and animals made by the methods are provided. Also provided are methods of screening for agents useful for treating a disease or disorder using mitochondrial-nuclear exchanged animals or cells, tissues or organs thereof.