2003 Fiscal Year Annual Research Report

ヒト発生過程におけるリムホメオボックス遺伝子(LHX)の解析

Research Project

Project/Area Number	13470343
Research Institution	Asahikawa Medical College
Principal Investigator	石川睦男旭川医科大学, 医学部, 副学長 (20002131)
Co-Investigator(Kenkyū-buntansha)	宮本敏伸旭川医科大学, 医学部, 助手 (70360998) 田熊直之旭川医科大学, 医学部, 助教授 (10312464) 山下剛旭川医科大学, 医学部, 講師 (30271787)
Keywords	LHX / 発生学 / ホメオボックス遺伝子 / Mbx / SYCP3 / 無精子症
Research Abstract	1.まず、発生過程に伴う遺伝子発現の変化を胎児と成人における子宮、卵巣、脳、肺、心臓、肝臓、腎臓、平滑筋の各組織でのLHX遺伝子群の発現の変化として解析した。発現の変化を認めたものとして、LHX1では肺および筋肉において胎児期に発現するものが成人で消失していた。LHX2では子宮において胎児期に認められた発現が、成人で消失していた。また腎臓では逆に成人でのみその発現が認められた。LHX3では肝臓、腎臓で胎児期に認められなかった発現が、成人になると発現が認められた。LHX4では肺、腎臓で同様に胎児期に認めなかった発現を成人で認めた。LHX9では肺、平滑筋において胎児期で発現するものが成人で消失していた。以上の基礎的検討から実際の検体を用いて検討するため、5例の死産流産患児よりDNAを抽出し遺伝子異常の有無を検索した。その結果LHX遺伝子の上流および下流遺伝子に欠損が認められず、LHX遺伝子にのみ異常のあったケースはLHX2,LHX3,LHX9であった。LHX2は造血器の形成、LHX3は下垂体の形成に関与し、LHX9は卵巣の形成に関与すると考えられており、これらの遺伝子は死産流産に伴いLHX遺伝子のみが欠損した可能性があることから、これらの欠損が死産流産に何らかの影響を及ぼした可能性を示唆することが示された。 2.Mbx遺伝子は全く新しいタイプのホメオボックス遺伝子である。共同研究機関であるNIHでのノックダウン法による解析で、Mbx遺伝子をノックダウンされたzebrafishはその生命には異常をきたさないが、その両眼及び中脳蓋のサイズは明らかな縮小を示すことを明らかにした。そこで我々はマウスcDNAを単離し、その発現が胎齢9.5日まではその中脳に限局していることを発表した。 3.更に我々は新たなヒト無精子症原因遺伝子SYCP3の同定に成功し、Lancetに発表した。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Toshinobu Miyamoto: "Azoospermia in patients heterozygous for a mutation in SYCP3"Lancet. 362. 1714-1719 (2003)
[Publications] Toshinobu Miyamoto: "Molecular cloning and expression analysis of the mouse Spot-2 gene in pituitary development"Dev Genes Evol. 213. 199-202 (2003)
[Publications] Toshinobu Miyamoto: "Isolation and Expression analysis of the human testis-specific gene, SPERGEN-1, a Spermatogenic Cell-Specific Gene-1"J Assist Reprod Genet. 20・2. 101-104 (2003)
[Publications] Toshinobu Miyamoto: "Isolation and expression analysis of the testis-specific gene, STRA8, stimulated by retinoic acid gene 8"J Assist Reprod Genet. 19・11. 531-535 (2002)
[Publications] Toshinobu Miyamoto: "Molecular cloning and expression analysis of MPP alpha-2, a novel mouse transcript detected in a differential screen of pituitary libraries"Biochim Biophys Acta. 1577・1. 109-112 (2002)
[Publications] Toshinobu Miyamoto: "Mbx, a novel mouse homeobox gene"Dev Genes Evol. 212・2. 104-106 (2002)
[Publications] Hiroaki Hayashi: "Cefpirome sulphate for gynaecological infections and prophylaxis of nonlaparotomy surgery in patients with benign disease"Int J Antimicrob Agents. 19・5. 405-411 (2002)
[Publications] Dibara S: "Effects of supplementation with free radical scavengers on the survival and fertilization rates of mouse cryopreserved oocytes"Hum Reprod. 16・9. 1976-1981 (2001)
[Publications] Kazuo Sengoku: "Requirement of nitric oxide for murine oocyte maturation, embryo development, and trophoblast outgrowth in vitro"Mol Reprod Dev. 58・3. 262-268 (2001)
[Publications] Yuichi Sato: "Overexpression of N-acetylglucosaminyltransferase III enhances the epidermal growth factor-induced phosphorylation of ERK in HeLaS3 cells by up-regulation of the internalization rate of the receptors"J Biol Chem. 276・15. 11956-11962 (2001)
[Publications] J Kamimura: "Identification of eight novel NSD1 mutations in Sotos syndrome"J Med Genet. 40・11. c126 (2003)
[Publications] Toshinobu Miyamoto: "Isolation and expression analysis of the human RNH2 gene encoding ribonuclease inhibitor 2"J Assist Reprod Genet. 19・8. 394-397 (2002)
[Publications] Toshinobu Miyamoto: "The human ASCL2 gene escaping genomic imprinting and its expression pattern"J Assist Reprod Genet. 19・5. 240-244 (2002)
[Publications] Pan B: "The soluble and membrane-anchored forms of heparin-binding epidermal growth factor-like growth factor appear to play opposing roles in the survival and apoptosis of human luteinized granulosa cells"Mol Hum Reprod. 8・8. 734-741 (2002)
[Publications] Keiko Tsuchiya: "A cytogenetic study of in-vitro matured murine oocytes after ICSI by human sperm"Hum Reprod. 17・2. 420-425 (2002)
[Publications] Mutsuo Ishikawa: "The clinical usefulness of salivary progesterone measurement for the evaluation of the corpus luteum function"Gynecol Obstet Invest. 53・1. 32-37 (2002)
[Publications] Yasuhito Kato: "Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells"Oncol Rep. 9・3. 565-569 (2002)

2003 Fiscal Year Annual Research Report

ヒト発生過程におけるリムホメオボックス遺伝子(LHX)の解析

Principal Investigator

石川 睦男 旭川医科大学, 医学部, 副学長 (20002131)

Research Products

[Publications] Toshinobu Miyamoto: "Azoospermia in patients heterozygous for a mutation in SYCP3"Lancet. 362. 1714-1719 (2003)

[Publications] Toshinobu Miyamoto: "Molecular cloning and expression analysis of the mouse Spot-2 gene in pituitary development"Dev Genes Evol. 213. 199-202 (2003)

[Publications] Toshinobu Miyamoto: "Isolation and Expression analysis of the human testis-specific gene, SPERGEN-1, a Spermatogenic Cell-Specific Gene-1"J Assist Reprod Genet. 20・2. 101-104 (2003)

[Publications] Toshinobu Miyamoto: "Isolation and expression analysis of the testis-specific gene, STRA8, stimulated by retinoic acid gene 8"J Assist Reprod Genet. 19・11. 531-535 (2002)

[Publications] Toshinobu Miyamoto: "Molecular cloning and expression analysis of MPP alpha-2, a novel mouse transcript detected in a differential screen of pituitary libraries"Biochim Biophys Acta. 1577・1. 109-112 (2002)

[Publications] Toshinobu Miyamoto: "Mbx, a novel mouse homeobox gene"Dev Genes Evol. 212・2. 104-106 (2002)

[Publications] Hiroaki Hayashi: "Cefpirome sulphate for gynaecological infections and prophylaxis of nonlaparotomy surgery in patients with benign disease"Int J Antimicrob Agents. 19・5. 405-411 (2002)

[Publications] Dibara S: "Effects of supplementation with free radical scavengers on the survival and fertilization rates of mouse cryopreserved oocytes"Hum Reprod. 16・9. 1976-1981 (2001)

[Publications] Kazuo Sengoku: "Requirement of nitric oxide for murine oocyte maturation, embryo development, and trophoblast outgrowth in vitro"Mol Reprod Dev. 58・3. 262-268 (2001)

[Publications] Yuichi Sato: "Overexpression of N-acetylglucosaminyltransferase III enhances the epidermal growth factor-induced phosphorylation of ERK in HeLaS3 cells by up-regulation of the internalization rate of the receptors"J Biol Chem. 276・15. 11956-11962 (2001)

[Publications] J Kamimura: "Identification of eight novel NSD1 mutations in Sotos syndrome"J Med Genet. 40・11. c126 (2003)

[Publications] Toshinobu Miyamoto: "Isolation and expression analysis of the human RNH2 gene encoding ribonuclease inhibitor 2"J Assist Reprod Genet. 19・8. 394-397 (2002)

[Publications] Toshinobu Miyamoto: "The human ASCL2 gene escaping genomic imprinting and its expression pattern"J Assist Reprod Genet. 19・5. 240-244 (2002)

[Publications] Pan B: "The soluble and membrane-anchored forms of heparin-binding epidermal growth factor-like growth factor appear to play opposing roles in the survival and apoptosis of human luteinized granulosa cells"Mol Hum Reprod. 8・8. 734-741 (2002)

[Publications] Keiko Tsuchiya: "A cytogenetic study of in-vitro matured murine oocytes after ICSI by human sperm"Hum Reprod. 17・2. 420-425 (2002)

[Publications] Mutsuo Ishikawa: "The clinical usefulness of salivary progesterone measurement for the evaluation of the corpus luteum function"Gynecol Obstet Invest. 53・1. 32-37 (2002)

[Publications] Yasuhito Kato: "Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells"Oncol Rep. 9・3. 565-569 (2002)

石川睦男旭川医科大学, 医学部, 副学長 (20002131)