Detection of point mutation at C-terminal region of phagosomal coat protein (TACO) in patients with leprosy.
- Author:
Se Kon KIM
1
;
Tae Jin KANG
;
Byoung Chul KIM
;
Gue Tae CHAE
Author Information
1. Institute of Hansen,s disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Korea.
- Publication Type:Original Article
- Keywords:
TACO;
coro1a gene;
leucine zipper motif;
coiled-coil region;
U1 snRNP
- MeSH:
Bacteria;
Codon;
DNA;
Exons;
Healthy Volunteers;
Humans;
Introns;
Leprosy*;
Leucine;
Leucine Zippers;
Lysosomes;
Phagosomes;
Point Mutation*;
Ribonucleoprotein, U1 Small Nuclear;
RNA Splice Sites;
Tryptophan;
Vacuoles
- From:Korean Leprosy Bulletin
2003;36(1):11-26
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Mycobacteria, which are highly successful pathogen, resist delivary to lysosomes and instead survive within a specialized vacuole, the mycobacterial phagosome. The bacteria survive intracellularly because they are able to actively recruit and retain TACO ( tryptophane aspartate-containing coat protein ) at the mycobacterial phagosome, where it prevents lysosomal delivary in a cholesterol-dependent manner. In this study, we investigated the difference of TACO expression is whether related to mutant in coro1a gene in patients with leprosy and normal volunteer. First, we screened for detection of a mutant in the leucine zipper motif within the exon 11, and then in the exon 9 to 10, and finally in the coiled-coil region. Interestingly, single base substitutions ( point mutation ) presents at assembly site of U1 snRNP, around of 5' splice site in the intron 9, there are a C to T and G to A transition are at 9 bp and 14 bp downstream of 5' splice site, respectively, and both of it. Among the 3 types of polymorphism, frequency of a G to A transition is markedly increased in patients of lepromatous type, which are new cases or relapsed. Both a C to T and G to A transitions are found in 1 case of tuberculoid type and 2 cases in lepromatoue type, but not found in control group. The silent mutation in leucine zipper motif within the exon 11 is located at codon at 454 ( CTG-->CTA), which is 1st leucine from C-terminal among four leucine zipper. In coiled-coil region, no mutation is found in genomic DNA of patients with leprosy. Further, we will do functional study about the identified point mutation and will screen any possible mutation in the region of promotor and WD repeat.
