{"id":14178,"date":"2017-04-03T15:44:42","date_gmt":"2017-04-03T06:44:42","guid":{"rendered":"http:\/\/mus.brc.riken.jp\/ja\/?page_id=14178"},"modified":"2022-07-15T14:13:12","modified_gmt":"2022-07-15T05:13:12","slug":"apr_2017_mm","status":"publish","type":"page","link":"http:\/\/mus.brc.riken.jp\/ja\/mouse_of_month\/apr_2017_mm","title":{"rendered":"Regulatory function of nuclear protein I\u03baB-\u03b6 in inflammatory responses"},"content":{"rendered":"\n\n\n
\"RIKEN<\/td>\nApril 2017<\/span>
\nMouse of the Month<\/span><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\nRegulatory function of nuclear protein I\u03baB-\u03b6
\nin inflammatory responses<\/span><\/p>\n
B6.Cg-Nfkbiz<tm1.1Muta><\/i> (RBRC06410)<\/a>
\n\"201704\"<\/a><\/p>\n

Courtesy of Takashi Maruyama, Ph.D.<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\n

I\u03baB-\u03b6 is one of the members of nuclear I\u03baB family, which are characterized by the presence of ankyrin repeats. I\u03baB-\u03b6 interacts with NF-\u03baB and regulates its activation to enhance expression of secondary response genes encoding inflammatory mediators such as IL-6 (A). Mice lacking I\u03baB-\u03b6 develop Sj\u00f6gren\u2019s syndrome (SS)-like dacryoadenitis, conjunctivitis, and periocular dermatitis [1, 2]. Muta, Maruyama, and their colleagues generated conditional Nfkbiz<\/i> knockout mice in a C57BL\/6 background, in which exons 5-7 of the gene were flanked by loxP sites (B). It has reported that exon 7 including transcriptional activation domain, and it plays a crucial role for transcription [3]. Similar inflammatory phenotype was observed in Nfkbiz<\/i> floxed mice crossed with epithelial cell-specific Cre mice, but not in the hematopoietic cell-specific I\u03baB-\u03b6 knockout mice. Enhanced apoptosis in the epithelial cells was proven to be the cause of the SS-like phenotype [4]. The group also generated T cell-specific I\u03baB-\u03b6 knockout mice and revealed that TGF-\u03b2 stimulation to na\u00efve CD4+ T cells induced I\u03baB-\u03b6 expression, which resulted in decreased Ifng<\/i> gene expression, and that I\u03baB-\u03b6-deficient Tregs<\/sub> have a reduced immunoregulatory function. I\u03baB-\u03b6 is also critical for activation of natural killer cells, and Toll-like receptor-mediated class switch recombination in B cells [5-7]. Conditional knockout mice provide an opportunity to identify and characterize multiple functions of I\u03baB-\u03b6.<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
Depositor<\/td>\n:<\/td>\nTakashi Maruyama, Ph.D.
\nGraduate School of Medicine
\nGifu University<\/td>\n<\/tr>\n
Strain name<\/td>\n:<\/td>\nB6.Cg-Nfkbiz<tm1.1Muta><\/i><\/td>\n<\/tr>\n
RBRC No.<\/td>\n:<\/td>\nRBRC06410<\/td>\n<\/tr>\n
References<\/td>\n:<\/td>\n[1]<\/td>\nKitamura H, Kanehira K, Okita K, Morimatsu M, Saito M. MAIL, a novel nuclear I kappa B protein that potentiates LPS-induced IL-6 production. FEBS Lett.<\/em>; 485(1):53-6, 2000.<\/a><\/td>\n<\/tr>\n
[2]<\/td>\nYamamoto M, Yamazaki S, Uematsu S, Sato S, Hemmi H, Hoshino K, Kaisho T, Kuwata H, Takeuchi O, Takeshige K, Saitoh T, Yamaoka S, Yamamoto N, Yamamoto S, Muta T, Takeda K, Akira S. Regulation of Toll\/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. Nature<\/em>; 430(6996):218-22, 2004.<\/a><\/td>\n<\/tr>\n
[3]<\/td>\nMotoyama M, Yamasaki S, Eto-Kimura A, Takeshige K, Muta T. Positive and negative regulation of nuclear factor-kappaB-mediated transcription by IkappaB-zeta, an inducible nuclear protein. J Biol Chem.<\/em> ; 280(9):7444-51, 2005.<\/a><\/td>\n<\/tr>\n
[4]<\/td>\n Okuma A, Hoshino K, Ohba T, Fukushi S, Aiba S, Akira S, Ono M, Kaisho T, Muta T. Enhanced apoptosis by disruption of the STAT3-I\u03baB-\u03b6 signaling pathway in epithelial cells induces Sj\u00f6gren’s syndrome-like autoimmune disease. Immunity<\/em>; 38(3):450-60, 2013.<\/a><\/td>\n<\/tr>\n
[5]<\/td>\nMaruYama T, Kobayashi S, Ogasawara K, Yoshimura A, Chen W, Muta T. Control of IFN-\u03b3 production and regulatory function by the inducible nuclear protein I\u03baB-\u03b6 in T cells. J Leukoc Biol.<\/em>; 98(3):385-93, 2015.<\/a><\/td>\n<\/tr>\n
[6]<\/td>\nMiyake T, Satoh T, Kato H, Matsushita K, Kumagai Y, Vandenbon A, Tani T, Muta T, Akira S, Takeuchi O. I\u03baB\u03b6 is essential for natural killer cell activation in response to IL-12 and IL-18. Proc Natl Acad Sci U S A.<\/em>; 107(41):17680-5, 2010.<\/a><\/td>\n<\/tr>\n
[7]<\/td>\nHanihara-Tatsuzawa F, Miura H, Kobayashi S, Isagawa T, Okuma A, Manabe I, MaruYama T. Control of Toll-like receptor-mediated T cell-independent type 1 antibody responses by the inducible nuclear protein I\u03baB-\u03b6. J Biol Chem.<\/em>; 289(45):30925-36, 2014.<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
April 2017
\nContact: Shinya Ayabe, Ph.D.<\/a>
\nExperimental Animal Division, RIKEN BioResource Center
\nAll materials contained on this site may not be reproduced, distributed, displayed, published or broadcast without the prior permission of the owner of that content.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

April 2017 Mouse of the Month   Regulatory function of nuclear protein I\u03baB-\u03b6 in inflammatory responses B6.Cg-Nfkbiz<tm1.1Muta> (RBRC06410) Courtesy of Takashi Maruyama, Ph.D.   I\u03baB-\u03b6 i […]<\/p>\n","protected":false},"author":19,"featured_media":0,"parent":198,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","_seopress_robots_follow":"","_seopress_robots_imageindex":"","_seopress_robots_snippet":"","_seopress_robots_primary_cat":"","_seopress_robots_breadcrumbs":"","_seopress_robots_freeze_modified_date":"","_seopress_robots_custom_modified_date":"","_seopress_robots_canonical":"","_seopress_social_fb_title":"","_seopress_social_fb_desc":"","_seopress_social_fb_img":"","_seopress_social_fb_img_attachment_id":0,"_seopress_social_fb_img_width":0,"_seopress_social_fb_img_height":0,"_seopress_social_twitter_title":"","_seopress_social_twitter_desc":"","_seopress_social_twitter_img":"","_seopress_social_twitter_img_attachment_id":0,"_seopress_social_twitter_img_width":0,"_seopress_social_twitter_img_height":0,"_seopress_redirections_value":"","_seopress_redirections_enabled":"","_seopress_redirections_enabled_regex":"","_seopress_redirections_logged_status":"both","_seopress_redirections_param":"","_seopress_redirections_type":301,"_seopress_analysis_target_kw":"","footnotes":"","_wp_rev_ctl_limit":""},"class_list":["post-14178","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/14178","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/users\/19"}],"replies":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/comments?post=14178"}],"version-history":[{"count":7,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/14178\/revisions"}],"predecessor-version":[{"id":19155,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/14178\/revisions\/19155"}],"up":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/198"}],"wp:attachment":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/media?parent=14178"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}