Investigation of the molecular basis of Posterior Colum Ataxia and Retinitis Pigmentosa

Posterior Column Ataxia and Retinitis Pigmentosa (PCARP) is a very rare neurodegenerative syndrome with childhood-onset. The disorder is due to the selective degeneration of photoreceptors in the retina and sensory neurons in the posterior column of the spinal cord. It is characterized by sensory ataxia (loss of coordination) and retinitis pigmentosa (eye degeneration), resulting in abnormal gait and blindness by the third decade. PCARP is due to mutations in Flvcr1 (Feline Leukaemia Virus subgroup C Receptor 1) gene, a protein involved in the export of heme. The reason why a defect in a heme exporter lead to this disorder is still unknown. This project is aimed at investigating the molecular mechanisms by which mutations in Flvcr1 gene lead to the selective degeneration of photoreceptors in the neurosensory retina and sensory neurons in the posterior column of the spinal cord. The main objective of the project is to generate a cellular and a mouse model of the disorder that will allow the understanding of the molecular basis of the disease. The availability of good cellular and animal models of the disorder will be essential in future to develop appropriate therapeutic strategies.