C57BL/6とC3H/He間でのコンソミックマウス系統の作成

• Project/Area Number: 14657236
• Research Category: Grant-in-Aid for Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: 吉川 武男 独立行政法人理化学研究所, 分子精神科学研究チーム, チームリーダー (30249958)
• Co-Investigator(Kenkyū-buntansha): MEERABUX Joanne 独立行政法人理化学研究所, 分子精神科学研究チーム, 研究員
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: コンソミックマウス / 複雑遺伝疾患 / 精神疾患 / 近交系マウス / C57BL / 6 / C3H / He / 近郊系マウス

Research Abstract

コンソミックマウスとは、受容系統のある染色体丸ごと1本を供与系統の染色体で置き換えたマウスで、コンソミツク系統はこれまで一般的だったコンジェニック系統、リコンビナント・インブレッド系統の弱点を克服し利点を合わせ持ったものと言える。コンソミック系統が樹立されると、精神疾患を含めて多因子疾患の原因遺伝子の絞り込み・遺伝子の単離に非常に役立つ。我々は、C57BL/6(B6)とC3H/He(C3)マウス近交系間でそれぞれを受容系統、供与系統とした「表」・「裏」のコンソミックラインを染色体2番、4番、6番、8番、11番、14番、17番、X染色体について作成中である。N2世代、N4世代で「best male/female」個体を選択する「スピードコンソミック」という手法を用いるため、N5世代で目的の染色体がほぼ100%置き換わった系統が得られる予定である。
本年度は、N3世代個体を親系統に戻し交配して各染色体につき以下の数の雄を確保した(「表」+「裏」):染色体2番-51匹、4番-82匹、6番-92匹、8番-95匹、11番-107匹、14番-109匹、17番-70匹。全個体をゲノムワイドマーカー(80個のマイクロサテライト)を用いてタイピングして、best male(N4世代)を各染色体あたり2匹ずつ選択した。X染色体に関しては、N2世代を307匹(「表」+「裏」)作成し、やはり80個のゲノムワイドマイクロサテライトマーカーを用いてタイピングし、best female個体を「表」と「裏」につき各2匹ずつ選択した。
コンソミックマウスの作成は非常に大きなプロジェクトであり、本研究の2年間で我々の技術の確からしさが証明され、最終段階まで7合目あたりという地点に無事たどり着いた。この段階で、常染色体ラインについては精子凍結、X染色体ラインに関しては4分割胚を凍結保存し、将来に備えた。

Research Products

• [Publications] Yoshitsugu K. et al.: "Fine mapping of an isodicentric Y chromosomal breakpoint from a schizophrenic patient."Am J Med Genet Neuropsychiatric Genet. 116B. 27-31 (2003)
• [Publications] Iwayama-Shigeno Y. et al.: "Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese schizophrenic patients."Am J Med Genet Neuropsychiatric Genet. 118B. 20-24 (2003)
• [Publications] Ebihara M. et al.: "Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility."Am J Med Genet Neuropsychiatric Genet. 118B. 32-35 (2003)
• [Publications] Kikuchi M. et al.: "Two-step association analyses of the chromosome 18p11.2 region in schizophrenia detect a locus encompassing C18orf1."Mol Psychiatry. 8. 467-469 (2003)
• [Publications] Toyota T. et al.: "Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees : a family-based association study."Neurosci Lett. 339. 5-8 (2003)
• [Publications] Arinami T. et al.: "Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-pair Linkage Group (JSSLG) families."Am J Med Genet Neuropsychiatric Genet. 120B. 22-28 (2003)
• [Publications] Itokawa M. et al.: "A microsatellite repeat in the promoter of the NMDA receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia."Pharmacogenetics. 13. 271-278 (2003)
• [Publications] Segurado R. et al.: "Genome scan meta-analysis of schizophrenia and bipolar disorder part III : bipolar disorder."Am J Hum Genet. 73. 49-62 (2003)
• [Publications] Itokawa M. et al.: "Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans."Neurosci Lett. 345. 53-56 (2003)
• [Publications] Yamada K. et al.: "Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders."Neurosci Lett. 349. 9-12 (2003)
• [Publications] Kikuchi M. et al.: "C18orf located on chromosome 18p11.2 may confer susceptibility to schizophrenia."J Med Dent Sci. 50. 225-229 (2003)
• [Publications] Ebihara T. et al.: "Structural characterization and promoter analysis of human potassium channel Kv8.1 (KCNV1) gene."Gene. 325. 89-96 (2004)
• [Publications] Arai M.et al.: "Association of neural cell adhesion molecule 1.gene polymorphisms with bipolar affective disorder in Japanese."Biol Psychiatry. (in press). (2004)
• [Publications] Yamada K. et al.: "Family-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3."Am J Med Genet Neuropsychiatr Genet. (in press). (2004)
• [Publications] Toyota T. et al.: "Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B."Hum Mol Genet. (in press). (2004)
• [Publications] Itokawa M. et al.: "Matsushita M Identification of a male schizophrenic patient carrying a de novo balanced translocation, t(4;13)(p16.1;q21.31)."Psychiatry Clin Neurosci. (in press). (2004)
• [Publications] Nakatani N. et al.: "Comprehensive expression analysis of a rat depression model."Pharmacogenomics J. (in press). (2004)
• [Publications] Toyota, T.et al.: "Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders"American Journal of Medieal Genetics, Neuropsychiatric Genetics. 114. 84-92 (2002)
• [Publications] Yoshikawa, T.et al.: "Identification of multiple genetic loci linked to the propensity for "behavioral despair" in mice"Genome Research. 12. 357-366 (2002)
• [Publications] Akanuma, N.et al.: "Interictal schizophrenia-like psychosis in a patient with double cortex syndrome"The Journal of Neuropsychiatry and Clinical Neurosciences. 14. 210-213 (2002)
• [Publications] Reyes, G.D.et al.: "Map of candidate genes and STSs on 18p11.2, a bipolar disorder and schizophrenia susceptibility region"Molecular Psychiatry. 7. 337-339 (2002)
• [Publications] Hattori, E.et al.: "An association study of the short tandem repeat in the 5'upstream region of the cholecystokinin gene with mood disorders in the Japanese population"American Journal of Medical Genetics, Neuropsychiatric Genetics. 114. 523-526 (2002)
• [Publications] Toyota, T.et al.: "Association analysis of adenylate cyclase type 9 gene using pedigree disequilibrium test in bipolar disorder"Molecular Psychiatry. 7. 450-452 (2002)
• [Publications] Ebihara, M.et al.: "Genomic organization and promoter analysis of the human nicotinic acetyicholine receptor α6 subunit (CHNRA6) gene : Alu and other elements direct transcriptional repression"Gene. 298. 101-108 (2002)
• [Publications] Ohtsuki, T.et al.: "Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees"Mol. Psychiatry. 7. 954-961 (2002)
• [Publications] Yoshitsugu, K.et al.: "Fine mapping of an isodicentric Y chromosomal breakpoint from a schizophrenic patient"American Journal of Medical Genetics, Neuropsychiatric Genetics. 116B. 27-31 (2003)
• [Publications] Iwayama-Shigeno, Y.et al.: "Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese schizophrenic patients"American Journal of Medical Genetics, Neuropsychiatric Genetics. (in press). (2003)
• [Publications] Ebihara, M.et al.: "Thanscriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility"American Journal of Medical Genetics, Neuropsychiatric Genetics. (in press). (2003)
• [Publications] Kikuchi, M.et al.: "Two step association analyses of the chromosome 18p11.2 region in schizophrenia detect a locus encompassing C18orf1"Molecular Psychiatry. (in press). (2003)