title: Identification of SP110 in horse (Equus caballus): Isolation of novel splice variants and evidence of activation effects on macrophages.
abstract: SP110 has previously shown to be a genetic determinant of host resistance to the intracellular pathogen infection in mouse and human. However, its relevant biological information in large non-primate animals still remains unknown. Here we report the novel discovery and characterization of three transcript variants of horse SP110. The transcript variant 1 (Tv1) of horse SP110 with the longest open reading frame has four domains (Sp100, SAND, PHD and Bromo domain). Tv2 and Tv3 share the same N-terminal sequence as Tv1, which contains Sp100 and SAND. We show that Tv2 is generated from alternative splicing and deletion of Exon17-Exon18 segment, while Tv3 is generated by pre-mature transcriptional termination at Exon 16. Furthermore, we demonstrate that the heterologous expression of horse SP110 variants stimulate macrophages into an activation-like phenotype. The macrophages underwent a shift in enhancing the secretion of cytokines (interleukin-1 (IL-1) and TNF-α) and accelerating inducible nitric oxide synthase (iNOS) activity, and eventually went into apoptotic cell death. Intriguingly, horse SP110 Tv1 showed more capability to trigger the immune activities compared to Tv2 and Tv3. To our knowledge, the identification of SP110 transcript variants from horse is the first report on biological function of SP110 in perissodactyla animals.
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Hengtao
authors.initials: H
authors.lastname: Ge
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Zekun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Quan
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address: zhyonglab@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006736:Horses; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D009169:Mycobacterium tuberculosis; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D016366:Open Reading Frames; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods; D013045:Species Specificity; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins
keywords: Apoptosis; Horse SP110; Macrophage activation; Mycobacterium tuberculosis; Native immune