Cell 173, 989–1002 (2018)

Knock-in of the huntingtin gene in pigs recreates key features of Huntington’s disease.

Huntington’s disease is a severe neurodegenerative monogenetic disease that results in age-dependent selective neuronal loss in affected individuals—a feature that cannot be mimicked in murine genetic models of the disease.

Collaborators from the United States and China used gene editing and somatic nuclear cell transfer to generate pigs expressing the huntingtin gene. Crucially, the added gene was inherited through the germline and resulted in age-dependent selective neuron loss mimicking human disease.

The work highlights the relevance of larger animal models to understanding this disease and developing therapeutics.