Identification of SP110 in horse (Equus caballus): Isolation of novel splice variants and evidence of activation effects on macrophages.

This study explores the role of SP110 in horses, revealing three versions of the gene and demonstrating their effect on immune cell activity, which can contribute to understanding the genetic factors influencing the ability to resist infections.

Identification of SP110 in Horses

• The researchers investigated the SP110 gene in horses. Previously, the gene was found to play a vital role in host resistance against infection in mice and humans. However, its function in large, non-primate animals like horses was not identified.
• The researchers discovered and characterized three new transcript variants of horse SP110, naming them Tv1, Tv2, and Tv3. Tv1 has the longest open reading frame and consists of four domains, namely Sp100, SAND, PHD, and Bromo domain.

Alternative Splicing and Premature Transcriptional Termination

• The study showed that Tv2 and Tv3 share the same N-terminal sequence with Tv1, which includes Sp100 and SAND. The researchers demonstrated how the two are generated using processes distinct from the formation of Tv1.
• Tv2 is created through alternative splicing and deletion of the Exon17-Exon18 segment, whereas Tv3 results from early transcriptional termination at Exon 16.

Activating Macrophages

• Through heterologous expression, researchers found that horse SP110 variants stimulate macrophages, an important cell type for the immune response, into an activity resembling activation.
• The activated macrophages amplified the secretion of cytokines (interleukin-1 (IL-1) and TNF-α) and accelerated inducible nitric oxide synthase (iNOS) activity, eventually leading to cell apoptosis (programmed cell death).

Differential Impact of SP110 Variants

• Interestingly, Tv1 of SP110 was seen to induce more significant immune activities compared to Tv2 and Tv3. This finding indicates that the different SP110 transcripts may have different influences on immune response effectiveness.
• The knowledge gained from this research provides the first insight into the biological function of SP110 in animals classified as perissodactyls, which include horses, zebras, and rhinoceroses, enhancing our understanding of immune response regulation and resilience to infection in these organisms.