Mouse model with a mutation in Arl13b to study medullablastoma formation.
Arl13b conditional mice preserve Gli repressor activity (protective against medullablastomas) and modulate the Gli activator (formation of medullablastoma).
Medullablastomas are the most common form of brain cancer in pediatric patients and about 30% of medullablastomas result from aberrant signaling processes that control cell fate and growth. More specifically, Sonic hedgehog signaling (Shh) is transmitted through cilia by the Gli protein family, which can either stimulate or repress target genes important for cell division. One hurdle in studying the role of Shh in medullablastomas is that removal of most ciliary proteins disrupts both the repressor and activator activities of the Gli proteins. The Caspary lab has developed a mouse model with a mutation in the Arl13b, a ciliary protein that affects Shh signaling uniquely and specifically. Mutations in the Arl13b mouse model show that the Gli repressor is normal and the Gli activator is not modulated, leading to low levels of activity. Therefore, the Arl13b mouse can suppress excess Gli activity and subvert tumor formation. Because the Gli repressor plays a protective role against medullablastomas and the Gli activator leads to the formation of medullablastomas, these mice provide a way to regulate tumor formation.
Mouse models have been created.