| Autor: |
K S Arnold, M E Balestra, R M Krauss, L K Curtiss, S G Young, T L Innerarity |
| Jazyk: |
angličtina |
| Rok vydání: |
1994 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 35, Iss 8, Pp 1469-1476 (1994) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1016/S0022-2275(20)40088-4 |
| Popis: |
Familial defective apolipoprotein B-100 (FDB) is a genetic disorder apparently caused by a single amino acid substitution (Arg3500–>Gln) that disrupts the binding of low density lipoproteins (LDL) to the LDL receptor. The plasma of FDB heterozygotes contains a mixture of normal LDL and LDL that is defective in binding to the LDL receptor. In this study, the monoclonal antibody MB19 (which recognizes an immunogenetic polymorphism in apolipoprotein B-100) was used to determine the percentage of defective LDL in the plasma of FDB heterozygotes and to isolate allele-specific receptor-binding-defective LDL. Several FDB heterozygotes were identified who were heterozygous for the MB19 polymorphism: one apolipoprotein B allotype in each of these individuals bound with low affinity to MB19 and possessed the Arg3500–>Gln mutation, whereas the other apolipoprotein B allotype bound with high affinity to MB19 and normally to the LDL receptor. Using MB19 radio-immunoassay, we determined that an average of 73% (range 65-87) of the total LDL from FDB heterozygotes contained the Arg3500–>Gln mutation. Antibody MB19-Sepharose immuno-affinity chromatography was used to separate the receptor-binding-defective LDL from the normal LDL. The isolated LDL contained primarily the Arg3500–>Gln mutation and had only about 9% of normal LDL receptor-binding ability. Finally, the MB19-Sepharose chromatography procedure may be useful for isolating other allele-specific LDL that have functionally significant mutations. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
