Identification of the causative genes and investigation of the molecular pathogenesis for skeletal dysplasias

• Project/Area Number: 20390408
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: FURUICHI Tatsuya The Institute of Physical and Chemical Research, 医学部, 講師 (30392103)
• Co-Investigator(Kenkyū-buntansha): IKEGAWA Shiro 独立行政法人理化学研究所, 骨間接疾患研究チーム, チームリーダー (30272496)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 骨系統疾患 / 遺伝子診断 / 小児運動器学

Research Abstract

We identified SLC39A13/ZIP13, TRIP11, CHST14, and SMOC1 as novel causative genes for skeletal dysplasias. We defined the spectrum of the diseases caused by SLC35D1, CANT1, and TRPV4 mutations. By using Zip13, Trip11, and Smoc1 mutant mice, we examined the disease-causing mechanisms by respective gene mutations. These findings should be useful to establish novel strategies for diagnosis and therapy of skeletal dysplasias.

Research Products

• [Journal Article] CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant. (2011)
  • Author(s): Furuichi T
  • Journal Title: J Med Genet. 48 Pages: 32-37
  • Peer Reviewed
• [Journal Article] SMOC1 is essential for ocular and limb development in humans and mice. (2011)
  • Author(s): Okada I, Furuichi T
  • Journal Title: Am J Hum Genet. 88 Pages: 30-41
  • Peer Reviewed
• [Journal Article] CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant (2011)
  • Author(s): Furuichi T
  • Journal Title: Journal of Medical Genetics Volume: 48 Pages: 32-37
  • Peer Reviewed
• [Journal Article] SMOC1 is essential for ocular and limb development in humans and mice (2011)
  • Author(s): Okada I
  • Journal Title: The American Journal of Human Genetics Volume: 88 Pages: 30-41
  • Peer Reviewed
• [Journal Article] Chondroitin sulfate N-acetylgalactosaminyl transferase-1 is required for normal cartilage development. (2010)
  • Author(s): Watanabe Y, Furuichi T
  • Journal Title: Biochem J. 432 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. (2010)
  • Author(s): Dai J, Furuichi T
  • Journal Title: J Med Genet. 47 Pages: 704-709
  • Peer Reviewed
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome. (2010)
  • Author(s): Miyake N, Furuichi T
  • Journal Title: Hum Mutat. 31 Pages: 966-974
  • Peer Reviewed
• [Journal Article] TRPV4-pathy, a novel channelopathy affecting diverse systems. (2010)
  • Author(s): Dai J, Ikegawa S
  • Journal Title: J Hum Genet. 55 Pages: 400-402
  • NAID: 10030735608
  • Peer Reviewed
• [Journal Article] Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. (2010)
  • Author(s): Nishimura G, Ikegawa S
  • Journal Title: Am J Med Genet. 152A Pages: 1443-1449
  • Peer Reviewed
• [Journal Article] A variant of Desbuquois dysplasia characterized by advanced carpal bone age, short metacarpals, and elongated phalanges : report of seven cases. (2010)
  • Author(s): Kim OH, Ikegwa S
  • Journal Title: Am J Med Genet. 152A Pages: 875-885
  • Peer Reviewed
• [Journal Article] Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210. (2010)
  • Author(s): Smits P, Ikegawa S
  • Journal Title: New Engl J Med. 362 Pages: 206-216
  • Peer Reviewed
• [Journal Article] Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development (2010)
  • Author(s): Watanabe Y
  • Journal Title: Biochemical Journal Volume: 25 Pages: 47-55
  • Peer Reviewed
• [Journal Article] Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family (2010)
  • Author(s): Dai J
  • Journal Title: Journal of Medical Genetics Volume: 47 Pages: 704-709
  • Peer Reviewed
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome (2010)
  • Author(s): Miyake N
  • Journal Title: Human Mutation Volume: 31 Pages: 966-974
  • Peer Reviewed
• [Journal Article] TRPV4-pathy, a novel channelopathy affecting diverse systems (2010)
  • Author(s): Dai J
  • Journal Title: Journal of Hum Genetics Volume: 55 Pages: 400-402
  • Peer Reviewed
• [Journal Article] Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations (2010)
  • Author(s): Nishimura G
  • Journal Title: American Journal of Medical Genetics Volume: 152A Pages: 1443-1449
  • Peer Reviewed
• [Journal Article] A variant of Desbuquois dysplasia characterized by advanced carpal Bone age, short metacarpals, and elongated phalanges : report of seven cases (2010)
  • Author(s): Kim OH
  • Journal Title: American Journal of Medical Genetics Volume: 152A Pages: 875-885
  • Peer Reviewed
• [Journal Article] Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210 (2010)
  • Author(s): Smits S
  • Journal Title: New England Journal of Medicine 363 Pages: 206-216
  • Peer Reviewed
• [Journal Article] Signaling mediated by the endoplasmic reticulum stress transducer OASISS is involved in bone formation. (2009)
  • Author(s): Murakami T, Furuichi T
  • Journal Title: Nat Cell Biol. 11 Pages: 1205-1211
  • Peer Reviewed
• [Journal Article] Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. (2009)
  • Author(s): Saito A, Furuichi T
  • Journal Title: Nat Cell Biol 11 Pages: 1197-1204
  • Peer Reviewed
• [Journal Article] Identification of loss-of-function mutations of SLC35D1 in patients with Schneckenbecken dysplasia, but not with other severe spondylodysplastic dysplasias group diseases. (2009)
  • Author(s): Furuichi T
  • Journal Title: J Med Genet. 46 Pages: 562-568
  • Peer Reviewed
• [Journal Article] Identification of loss-of-function mutations of SLC35D1 in patients with Schneckenbecken dysplasia, but not with other severe spondylodysplastic dysplasias group diseases (2009)
  • Author(s): 古市達哉
  • Journal Title: Journal of Medical Genetics 46 Pages: 562-568
  • Peer Reviewed
• [Journal Article] Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis (2009)
  • Author(s): Saito A
  • Journal Title: Nature Cell Biology 11 Pages: 1197-1204
  • Peer Reviewed
• [Journal Article] 蝸牛様骨盤異形成症の責任遺伝子SLC35Dの同定 (2009)
  • Author(s): 古市達哉
  • Journal Title: 第20回日本整形外科学会骨系統疾患研究会記録集 Pages: 31-34
• [Journal Article] The Zinc transporter SLC39A13/ZIP13 is required for connective tissue development ; Its involvement in BMP/TGF-β signaling pathways. (2008)
  • Author(s): Fukada T, Civic N, Furuichi T
  • Journal Title: PLoS One. 3
  • Peer Reviewed
• [Journal Article] A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotype of Desbuquosis dysplasia, diastrophic dysplasia and recessive form of multiple epiphyseal dysplasia. (2008)
  • Author(s): Miyake A, Furuichi T
  • Journal Title: J Hum Genet. 53 Pages: 764-768
  • Peer Reviewed
• [Journal Article] Association of the MSX2 gene polymorphisms with ankylosing spondylitis in Japanese. (2008)
  • Author(s): Furuichi T
  • Journal Title: J Hum Genet. 53 Pages: 419-424
  • NAID: 10021248849
  • Peer Reviewed
• [Journal Article] A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotype of recessive form of multiple epiphyseal dysplasia, diastrophic dysplasia and Desbuquosis dysplasia (2008)
  • Author(s): Miyake A
  • Journal Title: J Hum Genet 53 Pages: 764-768
  • Peer Reviewed
• [Journal Article] The Zinc transporter SLC39A13/ZIP13 is required for connective tissue development ; Its involvement in BMP/TGF-β signaling pathways (2008)
  • Author(s): Fukada T
  • Journal Title: PLoS One 3
  • Peer Reviewed
• [Journal Article] 糖ヌクレオチド輸送体SLC35D1は骨格形成に必須である (2008)
  • Author(s): 池川志郎
  • Journal Title: 実験医学 26 Pages: 913-916
• [Journal Article] 骨系統疾患と遺伝子異常-蝸牛様骨盤異形成症の原因遺伝子SLC35D1の発見- (2008)
  • Author(s): 池川志郎
  • Journal Title: 最新医学 63 Pages: 2211-2217
• [Presentation] 遺伝子改変マウスから見いだされた骨格異常を伴う新規トランスポーター病とその分子病態解析 (2010)
  • Author(s): 古市達哉
  • Organizer: 第38回北陸実験動物研究会
  • Place of Presentation: 富山
  • Year and Date: 2010-10-02
• [Presentation] 遺伝子改変マウスから見いだされた骨格異常を伴う新規トランスポーター病とその分子病態解析 (2010)
  • Author(s): 古市達哉
  • Organizer: 第38回北陸実験動物研究会
  • Place of Presentation: 富山(招待講演)
  • Year and Date: 2010-10-02
• [Presentation] ENUミュータジェネシスによる新規II型コラーゲン遺伝子(Col2a1)変異マウスの同定 (2010)
  • Author(s): 古市達哉
  • Organizer: 第150回日本獣医学会
  • Place of Presentation: 帯広
  • Year and Date: 2010-09-17
• [Presentation] From genome to skeletal diseases-recent advances in the association study of osteoarthritis and lumbar disc herniation and its association with ECM biology. (2010)
  • Author(s): 池川志郎
  • Organizer: Gordon Conference (Proteoglycan).
  • Place of Presentation: NH USA
  • Year and Date: 2010-07-14
• [Presentation] From genome to skeletal diseases-recent advances in the association study of osteoarthritis and lumbar disc herniation and its association with ECM biology (2010)
  • Author(s): Ikegawa S
  • Organizer: Gordon Conference (Proteoglycan)
  • Place of Presentation: New Hampshire, USA(Invited speech)
  • Year and Date: 2010-07-14
• [Presentation] ENUミュータジェネシスによる新規II 型コラーゲン遺伝子(Col2a1)変異マウスの同定 (2010)
  • Author(s): 古市達哉
  • Organizer: 第150回日本獣医学会
  • Place of Presentation: 帯広
• [Presentation] Novel and recurrent mutations in TRPV4 cause SMD, Kozlowski type and Metaropic dysplasia in Asians (2009)
  • Author(s): Dai Jin
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-25
• [Presentation] 亜鉛トランスポーター遺伝子ZIP13/SLC39A13の機能消失型変異は Ehlers-Danlos 症候群を引き起こす (2009)
  • Author(s): 古市達哉
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-24
• [Presentation] 糖ヌクレオチド輸送体SLC35D1は軟骨組織におけるコンドロイチン硫酸合成に必須であり、その機能欠損は重度な骨格形成不全を引き起こす (2009)
  • Author(s): 古市達哉、池川志郎
  • Organizer: 第1回新潟プロテオグリカン研究会
  • Place of Presentation: 新潟
  • Year and Date: 2009-03-06
• [Presentation] 亜鉛トランスポーター遺伝子ZIP13/SLC39A13の機能消失型変異はEhlers-Danlos症候群を引き起こす (2009)
  • Author(s): 古市達哉
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京
• [Presentation] Novel and recurrent mutations in TRPV4 cause SMD, Kozlowski type and Metaropic dysplasia in Asians. (2009)
  • Author(s): Dai J, 古市達哉
  • Organizer: 第54回日本人類遺伝学会.
  • Place of Presentation: 東京
• [Presentation] 大規模関連解析による変形性関節症感受性遺伝子の同定 (2009)
  • Author(s): 古市達哉、池川志郎
  • Organizer: 第82回日本生化学会シンポジウム : 「運動器」形成・再生のための分子基盤.
  • Place of Presentation: 神戸
• [Presentation] マウスとヒトの融合遺伝アプローチによる新規のトランスポーター病の同定とその分子病態の解明 (2009)
  • Author(s): 池川志郎、古市達哉
  • Organizer: 日本薬学会129年会 シンポジウム : 遺伝子改変マウスから見いだされたトランスポーター・チャンネルの新規機能
  • Place of Presentation: 京都
• [Presentation] Nucleotide-Sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human. (2009)
  • Author(s): 古市達哉
  • Organizer: The 26th Naito Conference : OSTEO BIOLOGY
  • Place of Presentation: Awaji-shima, Japan
• [Presentation] 蝸牛様骨盤異形成症の責任遺伝子SLC35D1の同定 (2008)
  • Author(s): 古市達哉
  • Organizer: 第20回日本整形外科学会骨系統疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-12
• [Presentation] 蝸牛様骨盤異形成症の責任遺伝子SLC35D1の同定 (2008)
  • Author(s): 古市達哉
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: 東京
• [Book] 後縦靭帯骨化症のモデルマウス～ttw(tiptoe walking)～(21) (2011)
  • Author(s): 池川志郎
  • Publisher: CLINICAL CALCIUM
• [Book] 第20回日本整形外科学会 骨系統疾患研究会記録集(蝸牛様骨盤異形成症の責任遺伝子SLC35D1の同定) (2009)
  • Author(s): 古市達哉、池川志郎
• [Book] 実験医学(26)(糖ヌクレオチド輸送体SLC35D1は骨格形成に必須である) (2008)
  • Author(s): 池川志郎、古市達哉
• [Book] 最新医学(63)(骨系統疾患と遺伝子異常-蝸牛様骨盤異形成症の原因遺伝子SLC35D1の発見-) (2008)
  • Author(s): 池川志郎、古市達哉、西村玄
• [Remarks]
  • URL: http://www.riken.jp/lab-www/OA-team/achieve.html
• [Remarks]
  • URL: http://www.riken.jp/lab-www/OA-team/index.html