Analysis of Polymorphisms in the Mediator Complex Subunit 13-like (Med13L) Gene in the Context of Immune Function and Development of Experimental Arthritis

• Published in: Archivum Immunologiae et Therapiae Experimentalis Vol. 66; no. 5; pp. 365 - 377
• Main Authors: Sardar, Samra, Kanne, Katrine, Andersson, Åsa
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2018; Springer Nature B.V
• Subjects: Animal models; Animals; Arthritis; Arthritis, Experimental - genetics; Arthritis, Rheumatoid - genetics; Autoantibodies - metabolism; Biomedical and Life Sciences; Biomedicine; Collagen; Collagen-induced arthritis; Computer applications; congenic mice; Data processing; Disease Models, Animal; Disease Susceptibility; Genetic Association Studies; Genetic Background; Genetic diversity; Genetic Predisposition to Disease; Genotype; Humans; Immune response; Immunology; Intellectual disabilities; MED13L; mediator complex; Mediator Complex - genetics; Mice; Mice, Congenic; Original; Original Article; Pharmacology/Toxicology; Phenotypes; Polymorphism, Genetic; Rheumatoid Arthritis; Rodents; THRAP2; Transcription; Congenic mice; Mediator complex; THRAP2; Collagen-induced arthritis; Rheumatoid arthritis; MED13L
• ISSN: 0004-069X; 1661-4917; 1661-4917
• DOI: 10.1007/s00005-018-0516-8

The Mediator complex subunit 13-like (MED13L) protein is part of the multi-protein mediator complex and plays an important role in gene transcription. Polymorphisms in the MED13L gene have been linked to congenital heart anomalies and intellectual disabilities. Despite recent evidence of indirect links of MED13L to cytokine release and inflammation, impact of genetic variations in MED13L on immune cells remains unexplored. The B10.RIII and RIIIS/J mouse strains vary in susceptibility to induced experimental autoimmune disease models. From sequencing data of the two mouse strains, we identified six polymorphisms in the coding regions of Med13L . Using congenic mice, we studied the effect of these polymorphisms on immune cell development and function along with susceptibility to collagen-induced arthritis, an animal model for rheumatoid arthritis. Combining in vivo disease data, in vitro functional data, and computational analysis of the reported non-synonymous polymorphisms, we report that genetic polymorphisms in Med13L do not affect the immune phenotype in these mice and are predicted to be non-disease associated.