Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice

被引：67

作者：

Erickson, RP ^{[1
]}

Garver, WS ^{[1
]}

Camargo, F ^{[1
]}

Hossian, GS ^{[1
]}

Heidenreich, RA ^{[1
]}

机构：

[1] Univ Arizona, Coll Med,Angel Char Children Wings Genet Res, Sect Med & Mol Genet,Dept Pediat, Steel Mem Childrens Res Ctr, Tucson, AZ USA

来源：

JOURNAL OF INHERITED METABOLIC DISEASE | 2000年 / 23卷 / 01期

关键词：

D O I：

10.1023/A:1005650930330

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

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页码：54 / 62

页数：9

相关论文

共 23 条

[1] Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis [J].

Carstea, ED ;

Morris, JA ;

Coleman, KG ;

Loftus, SK ;

Zhang, D ;

Cummings, C ;

Gu, J ;

Rosenfeld, MA ;

Pavan, WJ ;

Krizman, DB ;

Nagle, J ;

Polymeropoulos, MH ;

Sturley, SL ;

Ioannou, YA ;

Higgins, ME ;

Comly, M ;

Cooney, A ;

Brown, A ;

Kaneski, CR ;

BlanchetteMackie, EJ ;

Dwyer, NK ;

Neufeld, EB ;

Chang, TY ;

Liscum, L ;

Strauss, JF ;

Ohno, K ;

Zeigler, M ;

Carmi, R ;

Sokol, J ;

Markie, D ;

ONeill, RR ;

vanDiggelen, OP ;

Elleder, M ;

Patterson, MC ;

Brady, RO ;

Vanier, MT ;

Pentchev, PG ;

Tagle, DA .

SCIENCE, 1997, 277 (5323) :228-231

[2]

CHISOLM GM, 1988, AM J CARDIOL, V62, P20

[3] EFFECT OF VERAPAMIL AND NIFEDIPINE ON CHOLESTERYL ESTER METABOLISM AND LOW-DENSITY-LIPOPROTEIN OXIDATION IN MACROPHAGES [J].

DUSHKIN, MI ;

SCHWARTZ, YS .

BIOCHEMICAL PHARMACOLOGY, 1995, 49 (03) :389-397

[4] High-resolution mapping of the spm (Niemann-Pick Type C) locus on mouse Chromosome 18 [J].

Erickson, RP ;

Aviles, RA ;

Zhang, J ;

Kozloski, MA ;

Garver, WS ;

Heidenreich, RA .

MAMMALIAN GENOME, 1997, 8 (05) :355-356

[5] NORMAL PLASMA-LIPOPROTEINS AND FERTILITY IN GENE-TARGETED MICE HOMOZYGOUS FOR A DISRUPTION IN THE GENE ENCODING VERY-LOW-DENSITY LIPOPROTEIN RECEPTOR [J].

FRYKMAN, PK ;

BROWN, MS ;

YAMAMOTO, T ;

GOLDSTEIN, JL ;

HERZ, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8453-8457

[6] RAPID GENOTYPING OF LOW-DENSITY-LIPOPROTEIN RECEPTOR KNOCKOUT MICE USING A POLYMERASE CHAIN-REACTION TECHNIQUE [J].

GAW, A ;

MANCINI, FP ;

ISHIBASHI, S .

LABORATORY ANIMALS, 1995, 29 (04) :447-449

[7] BINDING-SITE ON MACROPHAGES THAT MEDIATES UPTAKE AND DEGRADATION OF ACETYLATED LOW-DENSITY LIPOPROTEIN, PRODUCING MASSIVE CHOLESTEROL DEPOSITION [J].

GOLDSTEIN, JL ;

HO, YK ;

BASU, SK ;

BROWN, MS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (01) :333-337

[8] Native and modified low density lipoproteins increase the functional expression of the macrophage class B scavenger receptor, CD36 [J].

Han, JH ;

Hajjar, DP ;

Febbraio, M ;

Nicholson, AC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (34) :21654-21659

[9]

Heidenreich RA, 1997, J RARE DIS, V3, P5

[10]

HEIDER JG, 1978, J LIPID RES, V19, P514