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Titolo:
UNEXPECTED CONSEQUENCES OF DELETION OF THE FIRST 2 REPEATS OF THE LIGAND-BINDING DOMAIN FROM THE LOW-DENSITY-LIPOPROTEIN RECEPTOR - EVIDENCE FROM A HUMAN MUTATION
Autore:
SASS C; GIROUX LM; LUSSIERCACAN S; DAVIGNON J; MINNICH A;
Indirizzi:
UNIV MONTREAL,CLIN RES INST MONTREAL,DEPT MED,HYPERLIPIDEMIA & ATHEROSCLEROSIS RES GRP MONTREAL PQ H2W 1R7 CANADA UNIV MONTREAL,CLIN RES INST MONTREAL,DEPT MED,HYPERLIPIDEMIA & ATHEROSCLEROSIS RES GRP MONTREAL PQ H2W 1R7 CANADA
Titolo Testata:
The Journal of biological chemistry
fascicolo: 42, volume: 270, anno: 1995,
pagine: 25166 - 25171
SICI:
0021-9258(1995)270:42<25166:UCODOT>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL HYPERCHOLESTEROLEMIA; LDL-RECEPTOR; ELECTROPHORETIC TRANSFER; GENE; CHOLESTEROL; PROTEINS; IDENTIFICATION; FIBROBLASTS; PLASMA; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
C. Sass et al., "UNEXPECTED CONSEQUENCES OF DELETION OF THE FIRST 2 REPEATS OF THE LIGAND-BINDING DOMAIN FROM THE LOW-DENSITY-LIPOPROTEIN RECEPTOR - EVIDENCE FROM A HUMAN MUTATION", The Journal of biological chemistry, 270(42), 1995, pp. 25166-25171

Abstract

Heterozygosity for a 5-kilobase (kb) deletion of the first two ligand-binding repeats (exons 2 and 3) of the low density lipoprotein (LDL) receptor (R) gene (LDL-R Delta 5kb) confers familial hypercholesterolemia (FH). The FH phenotype is unexpected based on previous site-directed mutagenesis showing that deletion of exons 2 and 3 resulted in little or no defect in LDL-R activity. In the present study, we took unique advantage of the ability to distinguish the LDL R Delta 5kb from thenormal receptor on the basis of size, in order to resolve this apparent discrepancy. Fibroblasts from heterozygotes for the LDL-R Delta 5kbdisplayed 50% of normal capacity to bind LDL and beta-VLDL, apparently due to lower receptor number, Cellular mRNA for the Delta 5kb allelewas at least as abundant as that for the normal allele. Immunoblotting and cell binding assays with anti-LDL-R antibody IgG-4A4 demonstrated normal synthesis and transport of the Delta 5kb receptor. Ligand blotting demonstrated that the Delta 5kb receptor displayed minimal or noability to bind LDL or beta-VLDL. Thus, in contrast to transfected cell lines, in human fibroblasts, the first two cysteine-rich repeats ofthe LDL-R appear functionally necessary. These characteristics of theLDL-R Delta 5kb in human fibroblasts explain the in vivo phenotype ofcarriers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 14:38:58