Doctor of Philosophy
Date of Defense
George T. Taylor
Infantile neuronal ceroid lipofuscinosis (INCL) is a lysosomal storage disease that is debilitating and fatal to children before their teenage years. The palmitoyl protein thioesterase 1 (PPT1) knockout (Ppt1-/-) mouse is an appropriate animal model that mimics much of the symptomology and brain pathology of the human disease. Ppt1-/- mice display blindness, seizures, and motor deficits and die well before wild-type mice. However, little is known about the cognitive and behavioral abilities of the Ppt1-/- mouse. This study was conducted to examine further the behavioral phenotype of the Ppt1-/- mouse model of INCL by evaluating the animals’ abilities in such domains as learning and memory, sensorimotor/motor coordination, and vision. To evaluate when behavioral symptoms become detectable, two ages of mice were included in the study. One cohort was tested beginning in the juvenile period (27 days old), and another cohort was tested beginning in adulthood (147 days old). Young Ppt1-/- mice showed no deficits in locomotor behavior, learning and memory, or vision compared to WT mice. However, Ppt1-/- juveniles may experience slight deficits in sensorimotor ability and motor coordination as indicated by decreased distance traveled in the running wheel test and slower swimming speeds during the Morris Water Maze. Adult Ppt1-/- mice exhibited more robust performance deficits, including decreased locomotor activity, worse performance during Morris Water Maze cued trials, decreased running wheel ability, and altered reactivity to fear conditioning. These older animals appeared to maintain normal vision and spatial learning ability. The results of this study expand our knowledge of the Ppt1-/- mouse model of INCL and provide novel information about the age of onset of behavioral symptoms. While the adult Ppt1-/- mice showed extensive behavioral deficits, some disease symptomatology was present even in the younger cohort. These results provide the grounds for examining Ppt1-/- mice at various ages on various domains, with the purpose of establishing solid behavioral markers to serve as benchmarks for disease progression and treatment efficacy.
Dearborn, Joshua Thomas, "Novel Behavioral Markers in the Ppt1-/- Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis" (2013). Dissertations. 284.