Recovery from liver disease in a Niemann-Pick type C mouse model

Naomi L. Sayre, Victoria M. Rimkunas, Mark J. Graham, Rosanne M. Crooke, Laura Liscum

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Loss of function of Niemann-Pick C1 (NPC1) leads to lysosomal free cholesterol storage, resulting in the neurodegenerative disease Niemann-Pick disease type C (NPC). Significant numbers of patients with NPC also suffer from liver disease. Currently, no treatments exist that alter patient outcome, and it is unknown if recovery from tissue damage can occur even if a treatment were found. Our laboratory developed a strategy to test whether mice can recover from NPC liver disease. We used antisense oligonucleotides to knock down hepatic expression of NPC1 in BALB/C mice for either 9 or 15 weeks. This recapitulated liver disease with hepatomegaly, cell death, and fibrosis. Then, antisense oligonucleotide treatment was halted for an additional 4, 9, or 15 weeks. We report that significant liver recovery occurred even when NPC1 protein expression only partially returned to normal. Several pathological phenotypes were alleviated, including hepatomegaly, cholesterol storage, and liver cell death. Histological examination revealed that foamy cell accumulation was relieved; however, liver fibrosis increased. Additionally, resolution of cholesterol storage and liver cell death took longer in mice with long-term knockdown.jlr Finally, we found that transcription of cholesterol homeostatic genes was significantly disrupted during the recovery phase after longterm knockdown.

Original languageEnglish (US)
Pages (from-to)2372-2383
Number of pages12
JournalJournal of lipid research
Issue number8
StatePublished - Aug 2010
Externally publishedYes


  • ATP-binding cassette G5
  • HMG CoA reductase
  • Liver X receptor
  • Lysosomal storage disease
  • Sterol responsive element binding protein-2

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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