| RRC ID |
51751
|
| 著者 |
Tohno M, Shinkai H, Toki D, Okumura N, Tajima K, Uenishi H.
|
| タイトル |
Identification of the Q969R gain-of-function polymorphism in the gene encoding porcine NLRP3 and its distribution in pigs of Asian and European origin.
|
| ジャーナル |
Immunogenetics
|
| Abstract |
The nucleotide-binding domain, leucine-rich-containing family, pyrin-domain containing-3 (NLRP3) inflammasome comprises the major components caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NLRP3. NLRP3 plays important roles in maintaining immune homeostasis mediated by intestinal microorganisms and in the immunostimulatory properties of vaccine adjuvants used to induce an immune response. In the present study, we first cloned a complementary DNA (cDNA) encoding porcine ASC because its genomic sequence was not completely determined. The availability of the ASC cDNA enabled us to reconstitute porcine NLRP3 inflammasomes using an in vitro system that led to the identification of the immune functions of porcine NLRP3 and ASC based on the production of interleukin-1β (IL-1β). Further, we identified six synonymous and six nonsynonymous single-nucleotide polymorphisms (SNPs) in the coding sequence of NLRP3 of six breeds of pigs, including major commercial breeds. Among the nonsynonymous SNPs, the Q969R polymorphism is associated with an increased release of IL-1β compared with other porcine NLRP3 variants, indicating that this polymorphism represents a gain-of-function mutation. This allele was detected in 100 % of the analyzed Chinese Jinhua and Japanese wild boars, suggesting that the allele is maintained in the major commercial native European breeds Landrace, Large White, and Berkshire. These findings represent an important contribution to our knowledge of the diversity of NLRP3 nucleotide sequences among various pig populations. Moreover, efforts to exploit the gain of function induced by the Q969R polymorphism promise to improve pig breeding and husbandry by conferring enhanced resistance to pathogens as well as contributing to vaccine efficacy.
|
| 巻・号 |
68(9)
|
| ページ |
693-701
|
| 公開日 |
2016-10-1
|
| DOI |
10.1007/s00251-016-0917-y
|
| PII |
10.1007/s00251-016-0917-y
|
| PMID |
27236661
|
| MeSH |
Animals
Apoptosis
Asian People / genetics*
Cloning, Molecular
HEK293 Cells
Humans
Inflammasomes / genetics*
NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
Polymorphism, Single Nucleotide / genetics*
Swine
White People / genetics*
|
| IF |
2.621
|
| 引用数 |
4
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
