Although testing candidate gene variants in zebrafish is rapid and can provide insight into gene function and biology and identify common pathways linked to a disease, there are limitations to studying OA per se in zebrafish.
To address some of the limitations of studying OA in zebrafish, we use the mouse to study the mammalian synovial joint and to introduce specific human disease alleles into the orthologous mouse genes. Generating a mouse model harboring a human disease allele is important to: 1. Define the functional significance of candidate disease causing alleles discovered in human studies, 2. Establish causal mechanism of action and 3. Identify disease modifying therapeutic treatments.
Edited Ripk2 allele using Crispr/Cas9 and a single stranded oligonucleotide as a donor molecule for homologous recombination.