Characterization of a novel porcine model of CLN3-Batten disease

CLN3-Batten disease is an autosomal-recessive disorder that results from mutations in CLN3. In the vast majority of cases, disease onset occurs in early childhood, is characterized by progressive loss of vision, seizures and a failure in psychomotor development and is universally fatal by the third decade of life. Several mouse models of CLN3 have been developed that have provided insight into the pathological progression of this disease including early glial activation followed by neuronal loss, however, many aspects of the disease are not recapitulated in these mouse models. Porcine models hold the promise of a more accurate disease model given the similarities that pigs and humans share in terms of development, anatomy, and physiology, and in particular, similarities in brain development such as perinatal growth spurt and brain structure. Furthermore, the shared characteristics of the human and porcine visual system make the pig a useful resource for studying macular-associated retinal diseases that are not possible in mice. Additionally, the size of the pig would allow for the use advanced neuroimaging techniques such as MRI, CT and/or PET to model in vivo changes within the CNS longitudinally and track the success of potential therapeutics. Recently, we have developed a novel CLN3 ∆ex7-8/∆ex7-8  porcine model of CLN3-Batten disease. Here we present initial characterization results showing behavioral, pathological, and visual deficits that mirror changes seen in human patients.