Basic improvement for Microminipigs: Preparation of MHC fixed pigs and analyses of the cellular immunological features

2013 Fiscal Year Final Research Report

• Project/Area Number: 23500502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokai University
• Principal Investigator: ANDO Asako 東海大学, 医学部, 非常勤准教授 (40101935)
• Co-Investigator(Kenkyū-buntansha): SHIINA Takashi 東海大学, 医学部, 准教授 (00317744) ; KITAGAWA Hitoshi 岐阜大学, 応用生物科学部, 教授 (70144003)
• Project Period (FY): 2011 – 2013
• Keywords: MHC / SLA / ミニブタ / MHC固定ブタ / ハプロタイプ / 中型実験動物

Research Abstract

To establish swine leukocyte antigen (SLA)-defined Microminipig (MMP) lines with extremely small sized novel miniature pigs, we characterized the polymorphic SLA alleles for three class I (SLA-1, SLA-2 and SLA-3) and two class II (SLA-DRB1 and -DQB1) genes in a MMP herd. Eleven SLA haplotypes including two novel ones, Hp-31.0 and Hp-0.37, and three recombinant haplotypes were found in the herd. In the eleven haplotypes, five homozygotes have been obtained by the breeding of heterozygous parents with each of the haplotypes. These homozygous animals will be useful to establish SLA defined MMP lines. To study cellular immunological responses in MMPs, alloreactivities of lymphocytes were assessed by the lymphocyte reaction (MLR) using the pigs with homozygous haplotypes. The strength of the proliferative responses of lymphocytes varied according to the combination of stimulator and responder cells with different haplotypes.

Research Products

• [Journal Article] Genomic sequence analysis of the major histocompatibility complex (MHC) class I G/F segment in common marmoset (Callithrix jacchus) (2014)
  • Author(s): Kono A, Brameier M, Roos C, Suzuki S, Shigenari A, Kametani Y, Kitaura K, Matsutani T, Suzuki R, Inoko H, Walter L, Shiina T
  • Journal Title: J Immunol Volume: 192 Pages: 3239-3246
• [Journal Article] HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by long range PCR and high throughput sequencing (2014)
  • Author(s): Ozaki Y, Suzuki S, Shigenari A, Okudaira Y, Kikkawa E, Oka A, Ota M, Mitsunaga S, Kulski JK, Inoko H, Shiina T
  • Journal Title: Tissue Antigens Volume: 83 Pages: 10-16
• [Journal Article] Genetic and family structure in a group of 165 common bottlenose dolphins caught off the Japanese coast (2013)
  • Author(s): Kita YF, Watanabe M, Tanaka A, Suzuki S, Ohizumi H, Hosomichi K, Iwasaki T, Ota M, Horie T, Inoko H, Kulski JK, Tanaka S. Shiina T
  • Journal Title: Mar Mam Sci Volume: 29 Pages: 474-496
• [Journal Article] Natural anti-insulin auto- antibodies in cats: Enzyme-linked immunosorbent assay for the determination of plasma anti-insulin IgG and its concentrations in domestic cats (2013)
  • Author(s): Takashima S, Nishii N, Hachisu T, Kojima M, Kigure-Hoshino M, Ogawa S, Suzuki T, Iwasawa A, Ohba Y, Kitagawa H
  • Journal Title: Research in Veterinary Science Volume: 95 Pages: 886-890
• [Journal Article] Identification and recombinant analysis of botorocetin-2, a snake venom cofactor for von Willebrand factor-induced platelet agglutination (2012)
  • Author(s): Yamamoto-Suzuki Y, Sakura Y, Fujimura Y, Matsumoto M, Hamako J, Kokubo T, Kitagawa H
  • Journal Title: Biochemistry Volume: 51 Pages: 5329 -5338
• [Journal Article] Study of cynomolgus monkey (Macaca fascicularis) Mhc DRB gene polymorphism in four populations (2012)
  • Author(s): Blancher A, Aarnink A, Tanaka K, Ota M, Inoko H, Yamanaka H, Nakagawa H, Apoil PA, Shiina T
  • Journal Title: Immunogenetics Volume: 64 Pages: 605-614
• [Journal Article] Super high resolution for single molecule- sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers (2012)
  • Author(s): Shiina T, Suzuki S, Ozaki Y, Taira H, Kikkawa E, Shigenari A, Oka A, Umemura T, Joshita S, Takahashi O, Hayashi Y, Paumen M, Katsuyama Y, Mitsunaga S, Ota M, Kulski JK, Inoko H
  • Journal Title: Tissue Antigens Volume: 80 Pages: 305-316
• [Journal Article] Porcine MHC classical class I genes are coordinately expressed in superantigen -activated mononuclear cells (2012)
  • Author(s): Kametani Y, Ohshima S, Kita YF, Shimada S, Kamiguchi H, Shiina T, Inoko H, Kulski JK, Ando A
  • Journal Title: Vet Immunol and Immunopathol Volume: 148 Pages: 252-259
• [Journal Article] Genetic variability in swine leukocyte antigen class II and Toll-like receptors affects immune responses to vaccination for bacterial infections in pigs (2012)
  • Author(s): Shinkai H, Arakawa A, Tanaka-Matsuda M, Ide-Okumura H, Terada K, Chikyu M, Kawarasaki T, Ando A, Uenishi H
  • Journal Title: Comp Immunol, Microbiol and Infect Dis Volume: 35 Pages: 523-532
• [Journal Article] Application of high- resolution, massively parallel pyrosequencing for estimation of haplotypes and gene expression levels of swine leukocyte antigen (SLA) class I genes (2012)
  • Author(s): Kita FY, Ando A, Tanaka K, Suzuki S, Ozaki Y, Uenishi H, Inoko H, Kulski JK, Shiina T
  • Journal Title: Immunogenetics Volume: 64 Pages: 187-199
• [Journal Article] 消化管近傍リンパ節に T 細胞性リンパ 細胞性リンパ 腫を発症した若齢犬の1 例 (2011)
  • Author(s): 高島 諭, 大場恵典, 渡邊一弘, 北川 均, 他
  • Journal Title: 日獣会誌 Volume: 64 Pages: 390-393
• [Journal Article] GM-CSF-Independent CD1a Expression in Epidermal Langerhans Cells: Evidence from Human CD1A Genome-Transgenic Mice (2011)
  • Author(s): Kobayashi C, Shiina T, Tokioka A, Hattori Y, Komori T, Kobayashi-Miura M, Takizawa T, Takahara K, Inaba K, Inoko H, Takeya M, Dranoff G, Sugita M
  • Journal Title: J Invest Dermatol Volume: 132 Pages: 241-244
• [Journal Article] Comparative genome analysis of the major histocompatibility complex (MHC) class I B/C segments in primates elucidated by genomic sequencing in common marmoset (Callithrix jacchus) (2011)
  • Author(s): Shiina T, Kono A, Westphal N, Suzuki S, Hosomichi K, Kita YF, Roos C, Inoko H, Walter L
  • Journal Title: Immunogenetics Volume: 63 Pages: 485-499
• [Journal Article] 次世代シークエンサーRoche 454FLX を用いた MHC タイピング法と遺伝子発現解析法の開発 (2011)
  • Author(s): 北 夕紀, 安藤麻子, 田中景子, 猪子英俊, 椎名 隆, 細道一善, 上西博英
  • Journal Title: DNA 多型日本DNA多型学会編 Volume: 19 Pages: 223-229
• [Journal Article] SLA-DRB1 and -DQB1 genotyping by the PCR-SSOP-Luminex method (2011)
  • Author(s): Ando A, Shigenari A, Ota M, Sada M, Kawata H, Azuma F, Kojima-Shibata C, Nakajoh M, Suzuki K, Uenishi H, Kulski JK, and Inoko H
  • Journal Title: Tissue Antigens Volume: 78 Pages: 49-55
• [Presentation] 超小型実験動物用ブタの MHC ハプロタイプと生時および 50 日齢の体重との関連性 (2013)
  • Author(s): 安藤麻子, 今枝紀明, 上野景子, 金子直樹, 大島志乃, 宮本あすか, 河田寿子, 高須正規, 猪子英俊, 北川 均
  • Organizer: 第22回日本組織適合性学会大会
  • Place of Presentation: コラッセ福島, 福島
  • Year and Date: 20130914-16
• [Presentation] ブタ脂肪由来間葉系幹細胞の MHC Class I・II の発現と免疫調節機能 (2013)
  • Author(s): 稲永由紀子, 岩崎研太, 安藤麻子, 大西彰, 丸山彰一, 小林孝彰
  • Organizer: 第22回日本組織適合性学会大会
  • Place of Presentation: コラッセ福島, 福島
  • Year and Date: 20130914-16
• [Presentation] SS-SBT 法の開発 (3) : 実用化を目指した簡略化や迅速化に関する研究 (2013)
  • Author(s): 椎名 隆, 尾崎 有紀, 鈴木 進悟, 重成 敦子, 桝屋 安里, 吉川 枝里, 岡 晃, 太田正穂, 光永 滋樹, 猪子 英俊
  • Organizer: 第22回日本組織適合性学会大会
  • Place of Presentation: コラッセ福島, 福島
  • Year and Date: 20130914-16
• [Presentation] MMP の体重と SLA クラス II ハプロタイプの関係 (2013)
  • Author(s): 今枝紀明, 高島諭, 高須正規, 西飯直仁, 金子直樹, 上野景子, 安藤麻子, 北川均
  • Organizer: 第155回日本獣医学会学術集会
  • Place of Presentation: 北海道大学高等教育推進機構, 札幌
  • Year and Date: 20130909-12
• [Presentation] Current Status of the Swine Leukocyte Antigen (SLA) Nomenclature System (2013)
  • Author(s): Essler S, Ando A, Rogel- Gaillard C, Lee JH, Lunney JK, Schook LB, Smith DM, Ho CS
  • Organizer: 10 th International Veterinary Immunology Symposium
  • Place of Presentation: Universit à degli Studi di Milano, Milan, Italy
  • Year and Date: 20130828-0901
• [Presentation] ブタ c-kit に対するモノクローナル抗体作製と性状解析 (2013)
  • Author(s): 大島志乃, 森修弥, 重成敦子, 高須正規, 今枝紀明, 布村聡, 田中正史, 北川均, 安藤麻子, 亀谷美恵
  • Organizer: 第60回日本実験動物学会総会
  • Place of Presentation: つくば国際会議場, つくば
  • Year and Date: 20130515-17
• [Presentation] Development of super high resolution single molecule sequence based typing (SS-SBT) method at the field 4 level without ambiguity (2013)
  • Author(s): Shiina T, Ozaki Y, Suzuki S, Kikkawa E, Shigenari A, Oka A, Mitsunaga S, Ota M, Inoko H
  • Organizer: The 27th European Immunogenetics and Histocompatibility Conference
  • Place of Presentation: MECC Maastricht the Netherlands, Maastricht, Netherlands
  • Year and Date: 20130511-13
• [Presentation] ミニブタの SLA 解析とその利活用 (2013)
  • Author(s): 安藤麻子, 椎名 隆, 今枝紀明, 金子直樹, 北川 均
  • Organizer: 第1回日本先進医工学ブタ研究会シンポジウム
  • Place of Presentation: 大阪国際会議場, 大阪
  • Year and Date: 2013-11-12
• [Presentation] Analyses on HLA genome diversity by next generation sequencing. Centennial of Hashimoto Disease International Symposium II (2012)
  • Author(s): Shiina T, Inoko H
  • Organizer: 30th Anniversary 22th Hot Spring Harbor Symposium Medical Institute of Bioregulation Kyushu University, Post-Global COE International Symposium
  • Place of Presentation: ACROS Fukuoka, Fukuoka
  • Year and Date: 20121201-04
• [Presentation] HLA 研究の臨床応用を目指した8桁レベルHLAタイピング法の開発 (2012)
  • Author(s): 椎名 隆, 鈴木 進悟, 尾崎 有紀, 吉川 枝里, 重成 敦子, 光永 滋樹, 猪子 英俊
  • Organizer: 第21回日本組織適合性学会大会シンポジウム「HLAとウイルス-新しい臨床展開-」
  • Place of Presentation: 明治大学駿河台キャンパス, 東京
  • Year and Date: 20120915-17
• [Presentation] 超小型実験動物用ブタの MHC タイプと体重との関連性 (2012)
  • Author(s): 安藤麻子, 金子直樹, 今枝紀明, 大島志乃, 高須正規, 河田寿子, 猪子英俊, 北川 均
  • Organizer: 第21回日本組織適合性学会大会
  • Place of Presentation: 明治大学駿河台キャンパス, 東京
  • Year and Date: 20120915-17
• [Presentation] Actinobacillus pleuropneumoniae 及び豚丹毒ワクチン接種時の抗体応答と SLA 及び TLR 遺伝子型との関連 (2012)
  • Author(s): 新開浩樹, 荒川愛作, 松田麻衣子, 奥村華子, 寺田圭, 知久幹夫, 河原崎達雄, 安藤麻子, 上西博英
  • Organizer: 第21回日本組織適合性学会大会
  • Place of Presentation: 明治大学駿河台キャンパス, 東京
  • Year and Date: 20120915-17
• [Presentation] 新しい実験動物ブタ MMP の身体・内臓サイズ (2012)
  • Author(s): 辻英里子, 高須正規, 今枝紀明, 高木充, 山添和明, 伊藤祐典, 柴田早苗, 金子直樹, 安藤麻子, 北川均
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学, 盛岡
  • Year and Date: 20120914-16
• [Presentation] MMPではSLAハプロタイプ-0.37のホモ個体は産まれない (2012)
  • Author(s): 角 佳憲, 今枝紀明, 高島 諭, 松原達也, 西飯直仁, 金子直樹, 安藤麻子, 北川 均
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学, 盛岡
  • Year and Date: 20120914-16
• [Presentation] Assignment of SLA class II haplotypes and outcome of the heterozygous breeding in microminipigs (2012)
  • Author(s): Ando A, Kaneko N, Imaeda N, Kawata H, Ohshima S, Inoko H, Hamazato F, Kitagawa H
  • Organizer: 33 th Conference of the International Society for Animal Genetics (ISAG)
  • Place of Presentation: Cairns Convention Center, Australia
  • Year and Date: 20120715-20
• [Presentation] The Swine Leukocyte Antigen (SLA) Nomenclature System : Current Status after 10 Years of its Establishment (2012)
  • Author(s): Ho CS, Ando A, Essler S, Rogel- Gaillard C, Lee JH, Lunney JK, Schook LB, Smith DM
  • Organizer: The Swine Leukocyte Antigen (SLA) Nomenclature System: Current Status after 10 Years of its Establishment
  • Place of Presentation: Cairns Convention Center, Australia
  • Year and Date: 20120715-20
• [Presentation] Diversity studies of SLA haplotypes by targeted high- throughput resequencing (2012)
  • Author(s): Mach N, Moroldo M, Marthey S, Ando A, Lee JH, Ho CS, Lunney JK, Estelle J, Rogel-Gaillard C
  • Organizer: 33 th Confer Cence of the International Society for Animal Genetics (ISAG)
  • Place of Presentation: Cairns Convention Center, Australia
  • Year and Date: 20120715-20
• [Presentation] MMP:超小型実験用ブタの MHCタイプと体重との関連性 (2012)
  • Author(s): 安藤麻子, 金子直樹, 今枝紀明, 大島志乃, 高須正規, 河田寿子, 猪子英俊, 北川 均
  • Organizer: 第59回日本実験動物学会総会
  • Place of Presentation: 別府国際コンベンションセンター, 別府
  • Year and Date: 20120524-26
• [Presentation] MHC固定ブタ末梢血単核球の活性化によるSLA クラス I 遺伝子発現の動態解析 (2011)
  • Author(s): 大島志乃, 亀谷美恵, 北 夕紀, 椎名 隆, 神口 浩, 猪子英俊, 安藤麻子
  • Organizer: 第20回日本組織適合性学会大会
  • Place of Presentation: ツインメッセ静岡, 静岡
  • Year and Date: 20110828-30
• [Presentation] 抗病性育種の選抜家系における SLA タイプの特徴-SLA タイプと免疫関連形質との相関- (2011)
  • Author(s): 安藤麻子, 鈴木啓一, 河田寿子, 重成敦子, 柴田千尋, 中條 満, 北川 均, 猪子英俊, 上西博英
  • Organizer: 第20回日本組織適合性学会大会
  • Place of Presentation: ツインメッセ静岡, 静岡
  • Year and Date: 20110828-30
• [Presentation] カニクイザル MHC 多型情報基盤と生物医学研究への展開, シンポジウム「ゲノム科学から切り拓く新時代のライフサイエンス」 (2011)
  • Author(s): 椎名 隆
  • Organizer: 第20回日本組織適合性学会
  • Place of Presentation: ツインメッセ静岡, 静岡
  • Year and Date: 20110828-30
• [Presentation] Microminipigs: New SLA -defined pigs for biomedical research (2011)
  • Author(s): Ando A, Kaneko N, Imaeda N, Kawata H, Ohshima S, Inoko H, Hamazato F, Kitagawa H
  • Organizer: Swine in Biomedical Research International Conference
  • Place of Presentation: Hilton Hotel Chicago
  • Year and Date: 20110716-19
• [Presentation] Resequencing of the Entire HLA Regions for Elucidating Haplotype Generation (2011)
  • Author(s): Shiina T, Suzuki S, Tanaka K, Yamanaka H, Nakagawa H, Ota M, Inoko H
  • Organizer: SMBE2011
  • Place of Presentation: Kyoto University Clock Tower Centennial Hall, Kyoto
  • Year and Date: 20110626-30
• [Presentation] MHC 固定ブタ末梢血単核球の活性化による SLA発現動態の解析 (2011)
  • Author(s): 大島志乃, 亀谷美恵, 北 夕紀, 椎名 隆, 神口 浩, 猪子英俊, 安藤麻子
  • Organizer: 第58回日本実験動物学会総会
  • Place of Presentation: タワーホール船堀, 東京
  • Year and Date: 20110525-27