{"id":5236,"date":"2013-06-27T10:56:06","date_gmt":"2013-06-27T01:56:06","guid":{"rendered":"http:\/\/mus.brc.riken.jp:7301\/?page_id=5236"},"modified":"2021-04-07T13:18:39","modified_gmt":"2021-04-07T04:18:39","slug":"aug_2012_mm","status":"publish","type":"page","link":"http:\/\/mus.brc.riken.jp\/ja\/mouse_of_month\/aug_2012_mm","title":{"rendered":"August 2012 Lethal anemia and chronic polyarthritis caused by undigested mammalian DNA"},"content":{"rendered":"

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Lethal anemia and chronic polyarthritis caused by undigested mammalian DNA<\/em><\/strong><\/h2>\n
\u00a0\u00a0B6.129-Dnase2atm2Osa<\/sup><\/span>\/OsaRbrc RBRC04020<\/a><\/h5>\n
B6.129-Dnase2atm1Osa<\/sup> Ifnar1tm1Agt<\/sup><\/span>\/OsaRbrc RBRC04021<\/a><\/h5>\n
\"Lethal<\/a>
Courtesy of Dr. Shigekazu Nagata, Kyoto University<\/figcaption><\/figure>\n

E17.5 wild-type, DNase2a-\/-<\/sup><\/span> (DNase II-\/-<\/sup>), and DNase2a-\/-<\/sup>Ifnar1-\/-<\/sup><\/span> (DNase II-\/-<\/sup>IFN-IR-\/-<\/sup>) embryos are dissected free from the yolk sac. The DNase2a-\/-<\/sup><\/span> embryos appear normal except for severe anemia. Anemia is not seen in the DNase2a-\/-<\/sup>Ifnar1-\/-<\/sup><\/span> embryos, confirming that type I interferon produced in the DNase2a-\/-<\/sup><\/span> embryos causes the anemia.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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Lysosomes in macrophages carry various degrading enzymes that digest the cellular components of dead cells. DNase II is a deoxyribonuclease that digests DNA and has optimal activity under acidic condition. A large amount of undigested DNA is observed in macrophages in the fetal liver of DNase2a-\/-<\/sup><\/span> mouse embryos and in the bone marrow of inducible DNase2a<\/span>-deficient mice. Undigested DNA in the lysosomes activates macrophages to produce interferon-\u03b2, which causes lethal anemia in DNase2a-\/-<\/sup><\/span> embryos. Indeed, on E17.5, the number of red blood cells in DNase2a-\/-<\/sup><\/span> embryos is less than 10% of that observed in wild-type embryos [1, 2].\n<\/div>\n

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Inducible DNase2a<\/span>-deficient mice and double-mutant mice lacking DNase II and the type I interferon receptor both appear normal at birth, but develop chronic polyarthritis resembling human rheumatoid arthritis [2, 3]. Histology of the affected joints shows cartilage destruction accompanied by the formation of a pannus-like structure. Genes for inflammatory cytokines, including TNF-\u03b1, IL-1\u03b2, and IL-6, are activated in the joints, and the administration of antibodies against these cytokines prevents the disease [4]. These mice provide the opportunity to understand the role of DNase II in the pathogenesis of human arthritis.\n<\/div>\n

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Related strain<\/td>\n:<\/td>\nB6;129-Dnase2atm1Osa<\/sup><\/span>\/OsaRbrc RBRC01725<\/a><\/td>\n<\/tr>\n
Depositor<\/td>\n:<\/td>\nDr. Shigekazu Nagata
\nDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University<\/td>\n<\/tr>\n
References<\/td>\n:<\/td>\n[1]Kawane K, Fukuyama H, Kondoh G, Takeda J, Ohsawa Y, Uchiyama Y, Nagata S<\/span>. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science; 292(5521):1546-9, 2001<\/a>.
\n[2]Kawane K, Ohtani M, Miwa K, Kizawa T, Kanbara Y, Yoshioka Y, Yoshikawa H, Nagata S<\/span>. Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature; 443(7114):998-1002, 2006<\/a>.
\n[3]Yoshida H, Okabe Y, Kawane K, Fukuyama H, Nagata S<\/span>. Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. Nat Immunol; 6(1):49-56, 2005<\/a>.
\n[4]Kawane K, Tanaka H, Kitahara Y, Shimaoka S, Nagata S<\/span>. Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation. Proc Natl Acad Sci USA; 107(45):19432-7, 2010.<\/a>.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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August 2012contact: Shinya Ayabe, Ph.D.<\/a>
\nExperimental Animal Division, RIKEN BioResource Center<\/td>\n<\/tr>\n
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Lethal anemia and chronic polyarthritis caused by undigested mammalian DNA \u00a0\u00a0B6.129-Dnase2atm2Osa\/OsaRbrc RBRC04020 B6.129-Dnase2atm1Osa Ifnar1tm1Agt\/OsaRbrc RBRC04021 E17.5 wild-type, DNase2a-\/- (DNa […]<\/p>\n","protected":false},"author":8,"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":"","_seopress_redirections_param":"","_seopress_redirections_type":301,"_seopress_analysis_target_kw":"","footnotes":"","_wp_rev_ctl_limit":""},"class_list":["post-5236","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/5236","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\/8"}],"replies":[{"embeddable":true,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/comments?post=5236"}],"version-history":[{"count":12,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/5236\/revisions"}],"predecessor-version":[{"id":18567,"href":"http:\/\/mus.brc.riken.jp\/ja\/wp-json\/wp\/v2\/pages\/5236\/revisions\/18567"}],"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=5236"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}