title: Hypertrophy of lymphoid organs is a possible phenotypic characteristic of R420W mutation of the cardiac ryanodine receptor gene: a study using a knock-in mouse model.
abstract: Cardiac ryanodine receptor gene (RyR2) mutations sometimes result in sudden cardiac death due to fatal arrhythmias. N-terminal R420W mutation of RyR2 is known to show similar phenotypes to arrhythmogenic right ventricular cardiomyopathy and to cause juvenile sudden death. We previously reported two sudden death cases with the same R420W mutation. Interestingly, the cases showed hypertrophy of lymphoid organs such as the thymus and mesenteric lymph nodes. The present study examined whether R420W mutation of RYR2 causes hypertrophy of lymphoid organs by generating a mouse model carrying the mutation. Homozygous (RyR2(R420W/R420W)) mice showed significant increases in thymus and spleen weights but not in kidney, heart, and brain weights compared with wild-type mice. The mice also showed remarkable hypertrophy of mesenteric lymph nodes. Immunohistochemical study revealed that RyR2 protein was prominently expressed in epithelial cells of the thymic medulla in the thymus. These findings show that mice with R420W mutation of RyR2 exhibit hypertrophy of lymphoid organs. Sudden unexplained death cases with the mutation may display such findings at autopsy.
authors.affiliation: Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan. Electronic address: hnishio@hyo-med.ac.jp.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Department of Legal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan. Electronic address: noku@hyo-med.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okudaira
authors.affiliation: Laboratory of Allergy Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan. Electronic address: mkazu@hyo-med.ac.jp.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Laboratory of Allergy Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya 663-8501, Japan. Electronic address: tomo@hyo-med.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshimoto
authors.affiliation: Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku, Takatsuki 569-8686, Japan. Electronic address: leg017@art.osaka-med.ac.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku, Takatsuki 569-8686, Japan. Electronic address: koichisz@art.osaka-med.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006984:Hypertrophy; D007150:Immunohistochemistry; D008208:Lymphatic System / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D016207:Cytokines; D019837:Ryanodine Receptor Calcium Release Channel
keywords: Arrhythmia; Autopsy; Status thymicolymphaticus; Sudden death; Thymus