Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice.
Niemann-Pick type C (NPC) is a neurodegenerative disorder with somatically altered cholesterol metabolism. The NPC1 gene has recently been cloned and shown to have sequences shared with known sterol-sensing proteins. We have used a mouse model with a disrupted Npc1 gene to study two cholesterol-lowering drugs (nifedipine and probucol) and the effects of introducing a null mutation in the low-density lipoprotein receptor (LDLR). Although these treatments significantly ameliorated liver cholesterol storage, little effect on the onset of neurological symptoms was found.
Erickson
R P
RP
Angel Charity for Children-Wings for Genetic Research, Steele Memorial Children's Research Center, Department of Pediatrics, University of Arizona College of Medicine, Tucson, USA.
Garver
W S
WS
Camargo
F
F
Hossain
G S
GS
Heidenreich
R A
RA
D000818:Animals; D001812:Blood-Brain Barrier; D002784:Cholesterol / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009542:Niemann-Pick Diseases / Q000188:drug therapy* / Q000235:genetics; D009543:Nifedipine / Q000627:therapeutic use*; D011341:Probucol / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000502:physiology*
D011973:Receptors, LDL; D002784:Cholesterol; D009543:Nifedipine; D011341:Probucol