Cerebellar pathology and motor deficits in the palmitoyl protein thioesterase 1-deficient mouse

Shannon L. Macauley, David F. Wozniak, Catherine Kielar, Yun Tan, Jonathan D. Cooper, Mark S. Sands

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Infantile neuronal ceroid lipofuscinosis (INCL, Infantile Batten Disease) is an inherited, neurodegenerative lysosomal storage disorder. INCL is the result of a CLN1 gene mutation leading to a deficiency in palmitoyl protein thioesterase 1 (PPT1) activity. Studies in the forebrain demonstrate the PPT1-deficient mouse (PPT1-/-) mimics the clinical symptoms and underlying pathology of INCL; however, little is known about changes in cerebellar function or pathology. In this study, we demonstrate Purkinje cell loss beginning at 3 months, which correlates with changes in rotarod performance. Concurrently, we observed an early stage reactive gliosis and a primary pathology in astrocytes, including changes in S100β and GLAST expression. Conversely, there was a late stage granule cell loss, microglial activation, and demyelination. This study suggests that neuronal-glial interactions are the core pathology in the PPT1-/- cerebellum. In addition, these data identify potential endpoints for use in future efficacy studies for the treatment of INCL.

Original languageEnglish
Pages (from-to)124-135
Number of pages12
JournalExperimental Neurology
Issue number1
StatePublished - May 2009

Bibliographical note

Funding Information:
We would like to thank Neuroscience Associates (Knoxville, TN) for their consistent quality of silver degeneration staining. This work was supported by NIH grants (NS043105; MSS and NS41930; JDC), Ruth L. Kirschstein NRSA Fellowship (NS056728; SLM), grant support and a graduate studentship from the Batten Disease Support and Research Association (CK), and an NIH Neuroscience Blueprint Core Grant (P30 NS057105; DFW) to Washington University.


  • Astrocytes
  • Batten disease
  • Cerebellar mutant
  • Gliosis
  • Glutamine synthetase
  • Lysosomal storage disease
  • Neurodegeneration
  • Rotarod
  • Silver degeneration staining

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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