Mammalian Cellular Model Of Fibrodysplasia Ossificans Progressiva (FOP)

Mammalian Cellular Model Of Fibrodysplasia Ossificans Progressiva (FOP)

Fibrodysplasia Ossificans Progressiva (FOP) is a rare and severely disabling genetic disorder characterized by heterotopic ossification—abnormal bone formation in soft tissues—caused by a mutation in the ACVR1 gene. With an estimated global prevalence of approximately 900 cases, FOP typically presents in early childhood and often results in progressive immobility and lifelong confinement to a wheelchair. Due to its rarity, limited research exists on the underlying biology of FOP, making it challenging to develop effective therapies. Our research aims to create a cellular model of FOP using CRISPR-Cas9 genome editing to introduce the classical FOP-associated mutation in the ACVR1 gene. Specifically, we are performing site-directed mutagenesis to change the wild-type codon CGC (Arginine) to the mutant codon CAC (Histidine). To confirm whether the genome edit has occurred, we are utilizing polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR) to amplify and analyze the target gene at the DNA and mRNA levels. This model will enable the study of FOP pathogenesis at the molecular level and facilitate the identification of therapeutic targets to prevent the progression of abnormal ossification. Such work is critical, as current treatments only alleviate symptoms, and surgical removal of abnormal bone often worsens the condition.