Characterization of Fibroblast Cells Derived from a Patient with Infantile Neuronal Ceroid Lipofuscinosis

Infantile Neuronal Ceroid Lipofuscinosis (INCL) belongs to a family of pediatric neurodegenerative disorders collectively known as Batten Disease. INCL is caused by mutations in the palmitoyl protein thioesterase 1 (PPT1) gene, leading to retinal and CNS deterioration due to accumulation of autofluorescent storage materials in the lysosome.  Although advances have been made in modeling the disease in various organisms, the elucidation of defined mechanistic pathways responsible for disease pathology and effective treatment remains a challenge.  The goal of the present study is to characterize the cellular behavior of a human patient fibroblast cell line deficient in the PPT1 enzyme.  PPT1 deficient cells were derived from a donor with Tyr247His and Met1Ile compound heterozygous mutations.  The donor cells are characterized and compared to the two PPT1 expressing fibroblast cell lines, HFF and MRC-5, using assays of cell morphology, cell viability, and autofluorescent accumulations.  Future work aims to establish an Induced Pluripotent Stem Cell (iPSC) line using the Yamanaka technique, in order to continue studying the pathology of the disease.  Specifically, neural progenitor cells deriving from these iPSC cells will be characterized and compared to wild type iPSCs to assess cell morphology, cell viability, autofluorescent accumulations, and neuronal function and pathology.