Increased production of intestinal immunoglobulins in Syntenin-1-deficient mice

Abstract

Syntenin-1 is an intracellular PDZ protein that binds multiple proteins and regulates protein trafficking, cancer metastasis, exosome production, synaptic formation, and IL-5 signaling. However, the functions of Syntenin-1 have not yet been clearly characterized in detail, especially in vivo. In this study, we generated a Syntenin-1 knock out (KO) mouse strain and analyzed the role(s) of Syntenin-1 in IL-5 signaling, because the direct interaction of Syntenin-1 with the cytoplasmic domain of the IL-5 receptor α subunit and the regulation of IL-5 signaling by Syntenin-1 have been reported. Unexpectedly, the number of IL-5-responding cells was normal and the levels of fecal immunoglobulins were rather higher in the Syntenin-1 KO mice. We also found that IgA and IgM production of splenic B cells stimulated in vitro was increased in Syntenin-1 KO mice. In addition, we showed that a distribution of intestinal microbial flora was influenced in Syntenin-1 KO mice. Our data indicate that Syntenin-1 negatively regulates the intestinal immunoglobulin production and has a function to maintain the intestinal homeostasis in vivo. The analysis of Syntenin-1 KO mice may provide novel information on not only mucosal immunity but also other functions of Syntenin-1 such as cancer metastasis and neural development.

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

“…As reported previously by Tamura et al [28] using syntenin-1 -deficient mice, we did not observe any phenotypic differences (Supplementary Figure S1), embryonic lethality, developmental abnormalities, or adult sterility in our mda-9 −/− mice. Additionally, body weight changes up-to six months and various organ weights at 3 months were similar between mda-9 −/− and wild type (WT) C57BL/6 mice (data not shown).…”

“…The mda-9 −/− mouse model used in the present study was independently generated and characterized, corroborating the prior results that deletion of mda-9/syntenin in all tissues of the mouse is not lethal. In agreement with Tamura et al [28], we also hypothesize that the lack of mda-9/syntenin in this animal is probably compensated by another variant of Syntenin, such as Syntenin-2, thereby preventing this knockout from being lethal.…”

“…Tamura et al . first demonstrated that knockout of MDA-9 (syntenin-1; SDCBP) in mice was not embryonic lethal and mice that developed did not show obvious abnormalities when grown in pathogen-free conditions [28]. The mda-9 −/− mouse model used in the present study was independently generated and characterized, corroborating the prior results that deletion of mda-9/syntenin in all tissues of the mouse is not lethal.…”

“…Recently, Tamura et al . reported that mda-9 (syntenin-1 ) knockout mice exhibit abnormalities in immunoglobulin production and have a modified intestinal microbiota [28]. Current studies support the hypothesis that mda-9/syntenin is involved in multiple signaling cascades under both physiological and pathological conditions and these processes affect various phenotypes in a tissue/organ context-dependent manner.…”

“…transformed cells, the MDA-9/Syntenin protein is ubiquitously expressed in the mouse (in both developing and adult stages [28, 51]) and in adult human organs, e.g., skin, liver, gall bladder, colon (www.Proteinatlas.org). Tamura et al .…”