The Role of Qa-2, the Functional Homolog of HLA-G, in a Mouse Model of Behcet's Disease Induced by HSV Inoculation

HLA-G (human leukocyte antigen-G) is a nonclassical class I MHC molecule. HLA-G interacts with different natural killer (NK) cell receptors and is able to inhibit NK and T-cell cytotoxicity, as well as T-cell proliferation. An HLA-G 3741_3754 14-base pair insertion allele was significantly more frequent in Behcet's disease (BD), with ocular, arthritis, and CNS symptoms, than in controls. The insertion was related to lower serum levels of HLA-G. Individuals homozygous for the insertion allele (3741_3754*ins14/* found to have a ins14 genotype) were 2.7-times greater risk of BD than controls. Thus, it has been suggested that the HLA-G allelic variant is one of the genetic risk factors for BD. In this study, reduced levels of Qa-2, a murine nonclassical class I MHC molecule and a possible functional homolog of HLA-G, was associated with various BD-like symptoms in mice, and siRNA (small interfering RNA) treatment was used to inhibit Qa-2 RNA expression in order to detect changes in symptoms according to Qa-2 levels. RNA interference (RNAi) has exploded as a new approach to manipulate gene expression in mammalian systems. Qa-2 levels in granulocytes were lower in BD mice than in normal controls and lower in BD mice with ocular symptoms than those without ocular symptoms. Silencing Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times with 3-day intervals) specifically reduced Qa-2 levels and resulted in BD progression, with the development of symptoms, including ocular symptoms and arthritis. We demonstrated that this approach could be extended to the in vivo mouse model by showing that silencing Qa-2 results in deteriorated conditions in BD mice.

Author dc:creator

• 이, 미영

Contributors dc:contributor

• 손, 성향
• 대학원 의학과
• 200524198

• 베체트
• 베체트병
• 마우스 모델
• Qa-2 유전자
• Role of Qa-2
• HSV Inoculation
• HLA-G
• Qa-2
• siRNA

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000001958
000000001958

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/2336