A Mitochondria-Focused Mouse Model (OPA-1-/- mouse) to Accelerate Gastrointestinal Pathophysiology Research

The invention is two engineered OPA-1-/- mouse models that will help address the central role of mitochondrial structure-function dynamics in the mammalian intestine – a translationally critical, but extremely underdeveloped, resource. This mouse models harbor an intestine-specific disruption in OPA-1, a key mitochondrial membrane-associated protein, which will be useful in assessing how mitochondrial structure/interaction influences enteric pathogen disease and basic intestinal cell biology. This can be used by internal and external stakeholders to study gastrointestinal health and disease over the mammalian lifespan, extending research opportunities in anti-infective drug development, infection, nutrition, cancer, metabolic diseases, diabetes, gut-microbiome interactions, and One Health.

Background: 
While animal models, particularly mouse models, are commonly used in research, animal models with intestine-restricted mitochondrial structural defects have not been available until now. It is increasingly appreciated that microbial pathogens aggressively manipulate host mitochondria as a virulence strategy. With these new mouse models, for the first time, gastrointestinal health and disease can be investigated over the mammalian lifespan.

Applications: 

• Gastrointestinal health and disease research 
  • Investigate how mitochondrial structure/interaction influences enteric pathogen disease and basic intestinal cell biology
• Research: infection, nutrition, cancer, metabolic diseases, diabetes, gut-microbiome interactions
• Anti-infective drug development 

Advantages: 

• Only mouse model that allows gastrointestinal health and disease research
• Can be investigated over the full lifespan
• Two versions of the mouse model
• Addresses a critical and underdeveloped resource 
• Can be used by internal and external stakeholders