Genetic disorders caused by the aberration of TGF signaling pathway and extracellular matrix proteins

• Project/Area Number: 20590331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Nagasaki University
• Principal Investigator: KINOSHITA Akira Nagasaki University, 大学院・医歯薬学総合研究科, 助教 (60372778)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Transforming Growth Factorβ1 (TGFB1) / TGF受容体2型(TGFBR2) / モデルマウス / ES細胞 / 細胞外マトリックス / Camuratii-Enelmann Disease / Marfan syndrome Type II / transforming factor / TGF receptor type II / 細胞外マトリックスタンパク質 / キメラマウス / Camuratii-Engelmann Disease / Loeys-Dietz syndrome type 2B / transforming growth factor β1 / TGF受容体2型 / Marfan症候群タイプ2 / TGF-β1 / gene targeting / リアルタイムPCR法

Research Abstract

We previously reported that mutations in TGFB1 and TGFBR2 caused autosomal dominant disorders (Cammurati-Engelmann disease and Marfansyndrome type II). To reveal the relationship between unregulated production/adoption of extracellular matrix proteins andaberrant TGF signaling, I tried to establish model mice harboring mutant allelesofTgfb1orTgfbr2. However, all of chimera mice were infertile, and I could not accomplish this investigation program.

Research Products

• [Journal Article] Mutation and copy number analysis in paroxysmal kinesigenic dyskinesia families. (2011)
  • Author(s): Ono S, Yoshiura KI, Kurotaki N, Kikuchi T, Niikawa N, Kinoshita A
  • Journal Title: MovDisord. (Epub ahead of print).
• [Journal Article] Clinical application of fetal sex determination using cell-free fetal DNA in pregnant carriers of X-linked genetic disorders. (2011)
  • Author(s): Miura K, Higashi jima A, Shimada T, Miura S, Yamasaki K, Abe S, Jo O, Kinoshita A, Yoshida A, Yoshimura S, Niikawa N, Yoshiura KI, Masuzaki H
  • Journal Title: J Hum Genet. (Epub ahead of print).
  • NAID: 10030658849
• [Journal Article] Epidemiology of human papillomavirus genotypes in pregnant Japanese women. (2011)
  • Author(s): Yamasaki K, Miura K, Shimada T, Miura S, Abe S, Murakami M, Sameshima T, Fujishita A, Kotera K, Kinoshita A, Yoshiura KI, Masuzaki H
  • Journal Title: J Hum Genet. (Epub ahead of print).
  • NAID: 10030658951
• [Journal Article] Mutation and copy number analysis in paroxysmal kinesigenic dyskinesia families. (2011)
  • Author(s): Ono S., et al., (6人中6番目)
  • Journal Title: Movement Disorders Volume: (in press)
  • Peer Reviewed
• [Journal Article] Clinical application of fetal sex determinatioh using ce11-free fetal DNA in pregnant carriers of X-linked genetic disorders. (2011)
  • Author(s): Miura K., et al., (13人中8番目)
  • Journal Title: Journal of Human Genetics Volume: (in press)
  • Peer Reviewed
• [Journal Article] Epidemiology of human papillomavirus genotypes in pregnant Japanese women. (2011)
  • Author(s): Yamasaki K., et al., (12人中10番目)
  • Journal Title: Journal of Human Genetics Volume: (in press)
  • Peer Reviewed
• [Journal Article] Identification of Pregnancy-Associated MicroRNAs in Maternal Plasma. (2010)
  • Author(s): Miura K, Miura S, Yamasaki K, Higashijima A, Kinoshita A, Yoshiura KI, Masuzaki H
  • Journal Title: Clin Chem. 56(11) Pages: 1767-1771
• [Journal Article] The possibility of microarray-based analysis using cell-free placental mRNA in maternal plasma. (2010)
  • Author(s): Miura K, Miura S, Yamasaki K, Shimada T, Kinoshita A, Niikawa N, Yoshiura K, Masuzaki H
  • Journal Title: PrenatDiagn. 30(9) Pages: 849-861
• [Journal Article] Familial brain arteriovenous malformation maps to 5p13-q14, 15q11-q13 or 18p11: Linkage analysis with clipped fingernail DNA on high-density SNP array. (2010)
  • Author(s): Oikawa M, Kuniba H, Kondoh T, Kinoshita A, Nagayasu T, Niikawa N, Yoshiura KI
  • Journal Title: Eur J Med Genet. 53(5) Pages: 244-249
  • NAID: 120006984921
• [Journal Article] Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome. (2010)
  • Author(s): Takahata T, Yamada K, Yamada Y, Ono S, Kinoshita A, Matsuzaka T, Yoshiura K, Kitaoka T
  • Journal Title: J Hum Genet. 55(3) Pages: 142-146
  • NAID: 10030733893
• [Journal Article] A type of familial cleft of the soft palate maps to 2p24.2-p24.1 or 2p21-p12. (2010)
  • Author(s): Tsuda M, Yamada T, Mikoya T, Sogabe I, Nakashima M, Minakami H, Kishino T, Kinoshita A, Niikawa N, Hirano A, Yoshiura K
  • Journal Title: J Hum Genet. 55(2) Pages: 124-126
  • NAID: 10030733799
• [Journal Article] Identification of Pregnancy-Associated MicroRNAs in Maternal Plasma. (2010)
  • Author(s): Miura K., et al., (7人中5番目)
  • Journal Title: Clinical Chemistry Volume: 56(11) Pages: 1767-1771
  • Peer Reviewed
• [Journal Article] The possibility of microarray-based analysis using cell-free placental mRNA in maternai plasma. (2010)
  • Author(s): Miura K., et al., (8人中5番目)
  • Journal Title: Prenatal Diagnosis Volume: 30(9) Pages: 849-861
  • Peer Reviewed
• [Journal Article] Familial brain arteriovenous malformation maps to 5p13-q14, 15q11-q13 or 18p11 : Linkage analysis with clipped fingernail DNA on high-density SNP array. (2010)
  • Author(s): Oikawa M., et al., (7人中4番目)
  • Journal Title: European Journal of Human Genetics Volume: 53(5) Pages: 244-249
  • Peer Reviewed
• [Journal Article] TGFシグナル異常による骨・軟骨疾患-単一遺伝病からありふれた疾患まで (2010)
  • Author(s): 木下晃
  • Journal Title: 医学のあゆみ Volume: 234(10) Pages: 987-992
• [Journal Article] Novel mutations in the SIL1 gene in a Japanese pedigree with the Marinesco-Sjogren syndrome. (2010)
  • Author(s): Takahata T., et al.(8人中5番目)
  • Journal Title: Journal of Human Genetics 55(3)(in press) Pages: 142-146
  • Peer Reviewed
• [Journal Article] A type familial cleft of the soft palate maps to 2p24.2-p24.1 or 2p21-p12 (2010)
  • Author(s): Tsuda M, et al.(11人中8番目)
  • Journal Title: Journal of Human Genetics 55 Pages: 124-126
  • Peer Reviewed
• [Journal Article] Japanese map of the earwax gene frequency : a nationwide collaborative study by Super Science High School Consortium. (2009)
  • Author(s): Super Science High School Consortium.
  • Journal Title: J Hum Genet 54(9) Pages: 499-503
• [Journal Article] Molecular karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome. (2009)
  • Author(s): Kuniba H, Yoshiura K, Kondoh T, Ohashi H, Kurosawa K, Tonoki H, Nagai T, Okamoto N, Kato M, Fukushima Y, Kaname T, Naritomi K, Matsumoto T, Moriuchi H, Kishino T, Kinoshita A, Miyake N, Matsumoto N, Niikawa N
  • Journal Title: J Hum Genet. 54(5) Pages: 304-309
  • NAID: 10030730501
• [Journal Article] Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene. (2009)
  • Author(s): Miyazaki K, Mapendano CK, Fuchigami T, Kondo S, Ohta T, Kinoshita A, Tsukamoto K, Yoshiura K, Niikawa N, Kishino T
  • Journal Title: Gene. 432(1-2) Pages: 97-101
• [Journal Article] Japanese map of the ear wax gene frequency : a nationwide collaborative study by Super Science High School Consortium. (2009)
  • Author(s): Super Science High School Consortium
  • Journal Title: Journal of Human Genetics 54 Pages: 499-503
  • Peer Reviewed
• [Journal Article] Molecular Karyotyping in 17 patients and mutation screening in 41 patients with Kabuki syndrome. (2009)
  • Author(s): Kuniba, et al.(19人中16番目)
  • Journal Title: Journal of Human Genetics 54 Pages: 304-309
  • Peer Reviewed
• [Journal Article] Precision of high-throughput single-nucleotide polymorphism genotyping with fingernail DNA : comparison with blood DNA. (2008)
  • Author(s): Nakashima M, Tsuda M, Kinoshita A, Kishino T, Kondo S, Shimokawa O, Niikawa N, Yoshiura K
  • Journal Title: ClinChemi. 54(10) Pages: 1746-1748
• [Journal Article] Lack of C20orf133 and FLRT3 mutations in 43 patients with Kabuki syndrome in Japan. (2008)
  • Author(s): Kuniba H, Tsuda M, Nakashima M, Miura S, Miyake N, Kondoh T, Matsumoto T, Moriuchi H, Ohashi H, Kurosawa K, Tonoki H, Nagai T, Okamoto N, Kato M, Fukushima Y, Naritomi K, Matsumoto N, Kinoshita A, Yoshiura KI, Niikawa N
  • Journal Title: J Med Genet. 45(7) Pages: 479-480
  • NAID: 120006983369
• [Journal Article] Developmentally dynamic changes of DNA methylation in the mouse Snurf/Snrpn gene (2008)
  • Author(s): Miyazaki K., et al. (10人中6番目)
  • Journal Title: Gene 54 Pages: 1746-1748
  • Peer Reviewed
• [Journal Article] Precision of high-throughput single-nucleotide polymorphism genotyping with fingernail DNA : comparison with blood DNA (2008)
  • Author(s): Nakashima M., et al. (8人中3人目)
  • Journal Title: Clinical Chemistry 54 Pages: 1746-1748
  • Peer Reviewed
• [Journal Article] Lack of C20orf133 and FLRT3 mutations in 43 patients With Kabuki syndrome in Japan (2008)
  • Author(s): Kuniba, et al. (20人中18人目)
  • Journal Title: Journal of Medical Genetics 45 Pages: 479-480
  • Peer Reviewed
• [Journal Article] TGFシグナル異常による骨・軟骨疾患-単一遺伝病からありふれた疾患まで医学のあゆみ
  • Author(s): 木下晃
  • Journal Title: 234(10) Pages: 987-992
• [Presentation] 子宮内膜癌特異的microRNAの網羅的スクリーニング (2010)
  • Author(s): 城大空, ら, (11人中9番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-30
• [Presentation] HELLP症候群と関連した胎盤特異的microRNAの網羅的解析 (2010)
  • Author(s): 三浦清徳, ら, (11人中9番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-29
• [Presentation] 唇顎口蓋裂のGenome-wide association study (2010)
  • Author(s): 引田正宣, ら, (10人中9番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-29
• [Presentation] SFTPC遺伝子変異を認めた家族制肺線維証の一家系 (2010)
  • Author(s): 小野慎治, ら, (6人中3番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-29
• [Presentation] ウイルス感染防御遺伝子のコピー数多型とHPV持続感染に関する検討 (2010)
  • Author(s): 阿部修平, ら, (8人中3番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-29
• [Presentation] 全胞状奇胎に特異的なmicroRNAの網羅的スクリーニング (2010)
  • Author(s): 長谷川ゆり, ら, (11人中9番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-29
• [Presentation] 母体血中における胎盤特異的microRNA群の網羅的スクリーニング (2010)
  • Author(s): 東島愛, ら, (11人中9番目)
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 大宮ソニックシティー
  • Year and Date: 2010-10-29
• [Presentation] HELLP症候群と関連した胎盤特異的microRNAの網羅的解析 (2010)
  • Author(s): 三浦清徳, 東島愛, 三浦生子, 山崎健太郎, 阿部修平, 城大空, 長谷川ゆり, 中山大介, 木下晃, 吉浦孝一郎, 増崎英明
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] 唇顎口蓋裂のGenome-wide associationstudy (2010)
  • Author(s): 引田正宣, 津田雅由, 佐々木健作, 三嶋博之, 吉田和加, 夏目長門, 内山健志, 平野明喜, 木下晃, 吉浦孝一郎
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] SFTPC遺伝子変異を認めた家族制肺線維証の一家系 (2010)
  • Author(s): 小野慎治, 田中健之, 木下晃, 石田雅之, 森本浩之輔, 吉浦孝一郎
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] 子宮内膜癌特異的microRNAの網羅的スクリーニング (2010)
  • Author(s): 城大空, 三浦清徳, 東島愛, 三浦生子, 山崎健太郎, 阿部修平, 増崎雅子, 長谷川ゆり, 木下晃, 吉浦孝一郎, 増崎英明
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] ウイルス感染防御遺伝子のコピー数多型とHPV持続感染に関する検討 (2010)
  • Author(s): 阿部修平, 三浦清徳, 木下晃, 山崎健太郎, 三浦生子, 嶋田貴子, 吉浦孝一郎, 増崎英明
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] 全胞状奇胎に特異的なmicroRNAの網羅的スクリーニング (2010)
  • Author(s): 長谷川ゆり, 三浦清徳, 東島愛, 城大空, 阿部修平, 三浦生子, 増崎雅子, 山崎健太郎, 木下晃, 吉浦孝一郎, 増崎英明
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] 母体血中における胎盤特異的microRNA群の網羅的スクリーニング (2010)
  • Author(s): 東島愛, 三浦清徳, 三浦生子, 山崎健太郎, 阿部修平, 城大空, 長谷川ゆり, 中山大介, 木下晃, 吉浦孝一郎, 増崎英明
  • Organizer: 第55回日本人類遺伝学会
• [Presentation] ヒト疾患モデルとしてのinterferon regulatory factor 6遺伝子改変マウスの表現型解析 (2009)
  • Author(s): 木下晃, Brian C.Schutte, 吉浦孝一郎
  • Organizer: 第16回遺伝子診療学会
  • Place of Presentation: ホテル札幌ガーデンプレース
  • Year and Date: 2009-07-31
• [Presentation] 発作性運動誘発性アテトーゼ(PKC)の変異解析 (2009)
  • Author(s): 小野慎治, 菊池妙子, 木下晃, 小澤寛樹, 新川詔夫, 吉浦孝一郎
  • Organizer: 第54回日本人類遺伝学会
• [Presentation] ヒト疾患モデルとしてのinterferon regulatory factor 6遺伝子改変マウスの表現型解析 (2009)
  • Author(s): 木下晃, Brian C.Schutte, 吉浦孝一郎
  • Organizer: 第16回日本遺伝子診療学会
• [Presentation] 大規模SNPタイピングにおける爪DNAの有用性の検討 (2008)
  • Author(s): 中島 光子, 他(5人中3番目)
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-09-30
• [Presentation] C20orf133は歌舞伎メーキャップ症候群の責任遺伝子ではない (2008)
  • Author(s): 国場 英雄, 他(17人中15番目)
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-09-30
• [Remarks] ホームページ等