Genetically Engineered Mouse Model Case Study

Breast Milk IgG and Infant Health

Antibodies passed from the mother influence infant health. The Koch Lab wanted to generate a mouse model that would allow them to precisely analyze the role of a specific antibody isotype, immunoglobulin gamma or IgG. Specifically, Dr. Meghan Koch and her team sought to generate a mouse strain in which only IgG antibodies (and not other isotypes like IgA or IgM) can accumulate within breast milk. To do this, Koch decided to target the polymeric immunoglobulin receptor. Also known as PIgR, this receptor is required to transfer IgM and IgA into breast milk. PIgR-deficient mice should contain only IgG antibodies in their milk.
 

The Challenge

Though PIgR-deficient mice were previously generated by several academic labs, they proved impossible to obtain. Some labs no longer maintained the mice, while the mice in other labs bred poorly. Additionally, the original mice were generated using an older, sloppier genetic engineering strategy. The scientists had first ablated Pigr in a related mouse strain and then crossed this strain to mice from the background Koch wanted to study. Unfortunately, this approach allowed several genes neighboring Pigr to hitchhike to the new mouse strain. This could potentially confound interpretation of experimental results obtained in these animals.  
 

The Approach

• The core offered highly effective CRISPR/Cas9-based gene editing in mouse embryos with fast turnaround and sperm cryopreservation services.
• In particular, the core produced Pigr-KO mice in a C57BL/6 background not available through any commercial sources or investigators.
• The GEMM core also cryopreserved several other mouse strains.
• Always available for technical advice regarding experimental strategy, genotyping procedure, or breeding strategies, the core provided unprecedented support at all stages of the genome-editing work process, from target strategy to generation of transgenic systems.
  

The Outcome

The first set of litters includes several 'founder' strains that are deficient in PIgR expression. The Koch Lab will breed these mice to generate animals they can use to analyze pups reared by PIgR-deficient dams to determine how breast milk-derived maternal IgG antibodies impact neonatal immune responses to intestinal bacteria. 
 

Read More

Read more about the Koch Lab’s research.