Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein

Chonglun Xie, Stephen D. Turley, Peter G. Pentchev, John M. Dietschy

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Type C Niemann-Pick disease is due to a mutation in Niemann-Pick C (NPC) protein, a putative determinant of intracellular cholesterol transport. This study quantifies cholesterol balance in vivo across all tissues in mice with this defect. Cholesterol balance in the heterozygous animal is normal, but in the homozygous mouse the whole animal cholesterol pool expands continuously from birth, reaching 5,442 mg/kg at 7 wk. The size of this pool in each organ is proportional to the rate at which each tissue clears low-density lipoprotein-cholesterol. Despite this expansion, however, cholesterol synthesis is increased so that whole animal synthesis equals 180 mg · day- 1 · kg-1. Forcing additional cholesterol into the liver through the clathrin-coated pit pathway increases the hepatic cholesterol pool in control mice, all of which is esterified, while there is a much greater increase in this pool in mutant mice, all of which is unesterified. These findings are consistent with the view that there is a block in sterol movement from the lysosome to the sites of regulation in NPC disease and have important implications for understanding the function of the NPC protein in intracellular cholesterol metabolism, in general, and in the brain, in particular.

Original languageEnglish (US)
Pages (from-to)E336-E344
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 39-2
StatePublished - Feb 1999


  • Cholesterol synthesis
  • Endoplasmic reticulum
  • Low-density lipoprotein receptor
  • Lysosome
  • Neurodegeneration

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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