Transgenic Mouse Model Expressing microRNA34 for Accelerated Aging
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Solution Overview
Problem
Current animal models for accelerated aging and age-related symptoms, such as Alzheimer's disease, are inadequate for selecting candidate compounds for treating or preventing sporadic forms of these conditions, as they are primarily based on gene mutations associated with early-onset familial cases rather than sporadic cases.
Innovation Solution
Development of a transgenic non-human animal model expressing microRNA sequences miR-34a or miR-34c, which accelerates aging and exhibits age-related symptoms, allowing for the selection of therapeutic compounds by measuring circulating microRNA and target polypeptide levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If transgenic animal models are used to study accelerated aging, then aging processes can be accelerated and observed, but the models are based on gene mutations associated with early-onset familial cases rather than sporadic cases
Solution Approach 1:
The patent changes the genetic parameter from early-onset familial mutation models to sporadic case models by introducing transgenes that express microRNA sequences (miR-34a, miR-34c) and target polypeptides (Bcl-2, Presenilin-1) associated with sporadic aging and Alzheimer's disease. This parameter change makes the model more representative of human sporadic aging while maintaining accelerated aging speed.
2Productivity
If conventional animal models are used for drug screening, then compound selection can be performed, but the models are inadequate for selecting candidate compounds for treating sporadic forms of age-related conditions
Solution Approach 1:
The patent changes the biological parameter of the model from familial mutation-based to sporadic case-based by expressing microRNA sequences and target polypeptides that mimic human sporadic aging and Alzheimer's disease pathology. This enables accurate screening of compounds for sporadic forms while maintaining high productivity in compound evaluation.
3Speed
If microRNA sequences are expressed in transgenic animals, then aging is accelerated and age-related symptoms appear, but the complexity of the transgenic construct increases
Solution Approach 1:
The patent segments the transgenic construct into separate expression cassettes: one for microRNA sequences (miR-34a, miR-34c) and another for target polypeptides (Bcl-2, Presenilin-1). Each cassette can be independently designed, regulated by specific promoters, and validated. This segmentation reduces construct complexity while achieving accelerated aging and age-related symptoms.
Data Source
AI summary
A transgenic, non-human animal model for accelerated aging and/or age-related symptom, recombinant nucleic acid molecules, cells and methods that can be used to make such animal model and cells, methods of using the animal model and cells, to descendants of the transgenic non-human animal, obtained by breeding with the same or with another phenotype, and to a cell line or primary cell culture or to an organotypic brain slice culture, derived from the transgenic non-human animal or its descendants are disclosed.