NRIP Knockout Mouse Model for Muscle Dystrophy Research

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Solution Overview

Problem

Current understanding of muscular dystrophies is incomplete, and the role of nuclear receptor interaction protein (NRIP) in these disorders is not fully investigated, despite its down-regulation in muscular dystrophy patients and its potential impact on muscle function.

Innovation Solution

A transgenic NRIP knockout mouse is created by disrupting the NRIP gene, specifically deleting exon 2, to study the phenotype of abnormal muscular function and the relationship between NRIP and muscle dystrophy, involving gene targeting in mouse embryonic stem cells and breeding to produce homozygous knockout mice.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If NRIP gene is disrupted to create knockout mice, then the role of NRIP in muscle function can be investigated, but the complexity of the research model increases

Engineering Contradiction:

Improveunderstanding of NRIP role in muscle dystrophyVSAvoidcomplexity of transgenic mouse model

Core Design Contradiction:

Loss of informationVSDevice complexity

Solution Approach 1:

The NRIP gene disruption is achieved by deleting a specific segment (exon 2) rather than the entire gene, allowing targeted investigation of NRIP function while maintaining a manageable model complexity. This segmental approach enables focused study of the protein's role in muscle function without requiring complete gene elimination.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses transgenic embryonic stem cells as an intermediary system to generate the knockout mice. This intermediary approach allows controlled introduction of the gene disruption through standard genetic engineering protocols, facilitating the creation of the research model while following established methodologies.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Manufacturing precision

If exon 2 is deleted from NRIP gene, then specific phenotype of abnormal muscular function can be observed, but the manufacturing precision of the knockout model requires high accuracy

Engineering Contradiction:

Improveprecision of gene disruptionVSAvoidease of creating knockout mice

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The gene disruption is localized to exon 2 specifically, rather than affecting the entire NRIP gene uniformly. This local quality approach allows precise investigation of the deleted region's function while maintaining the rest of the gene structure, enabling focused phenotypic analysis with controlled precision requirements.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs preliminary gene targeting in embryonic stem cells before generating the knockout mice. This preliminary action establishes the gene disruption in a controlled cellular environment first, ensuring precision is achieved before propagating the model through breeding, thereby simplifying the overall manufacturing process.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS8729335B2NRIP knockout mice and uses thereof

Publication Date: 2014.05.20 NAT TAIWAN UNIV

AI summary

The present invention directs to a transgenic NRIP knockout mouse, the genome of which is manipulated to comprise a disruption of a nuclear receptor interaction protein (NRIP) gene, wherein the NRIP gene is disrupted by deletion of exon 2, the mouse exhibits a phenotype comprising abnormal muscular function. The present invention also directs to a method for making a transgenic NRIP knockout mouse whose genome comprises a homozygous disruption of the NRIP gene, the mouse exhibits abnormal muscular function.