Question

What is meant by 'Gene knock out'? How is it useful in developing mouse models for studying human diseases?

Hint:

Mario Capecchi, Martin Evans, and Oliver Smithies were awarded the Nobel Prize in Medicine in 2007 for their pioneering work on homologous recombination in mouse embryonic stem cells, which made the creation of knockout mice possible.

Answer 1

Step 1: Defining 'Gene Knock Out'
A gene knock out is a genetic engineering technique where a specific gene within an organism's genome is rendered completely inactive or inoperative ("knocked out"). This is typically achieved by disrupting the gene's protein-coding region through homologous recombination in embryonic stem cells, replacing the target gene with a marker gene (like neomycin resistance) to disrupt translation.

Step 2: Usefulness in Developing Mouse Models
Mice share approximately $99%$ of their protein-coding genes with humans, making them highly effective physiological models. Knockout mouse models are invaluable for studying human diseases for several reasons:
1. Investigating Gene Function: By systematically knocking out a gene, researchers can observe the resulting physiological defects, identifying the gene's normal biological role (loss-of-function analysis).
2. Modeling Human Pathologies: Many human genetic disorders (such as Cystic Fibrosis or Hemophilia) can be modeled in mice by inactivating the mouse homolog of the disease gene. This allows researchers to study the step-by-step progress of the disease in living tissue.
3. Pre-clinical Drug Screening: These knockout mice can be used to test new gene therapies, small-molecule drugs, and treatment approaches before starting human clinical trials.
Final Answer: A gene knock out involves inactivating a specific gene in an organism's genome. In mice, it is used to disable human-homologous genes to model human genetic diseases, study disease progress, and screen new therapies in vivo.