JP2015165780A - Mouse expressing egfp in thalamus-cortical axon - Google Patents
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Abstract
Description
本発明は、視床−皮質軸索の発達を検討可能なトランスジェニックマウス及びその作製方法に関する。 The present invention relates to a transgenic mouse capable of examining the development of thalamic-cortical axons and a method for producing the same.
大脳皮質は、大脳の表面に広がる、神経細胞の細胞体の密な灰白質の薄い層であり、知覚、随意運動、思考、推理、記憶など脳の高次機能を司る。一方、視床は、間脳の一部を占める部位であり、嗅覚を除く、視覚、聴覚、体性感覚などの感覚入力を大脳新皮質へ中継する重要な役割を担っている。 The cerebral cortex is a thin gray layer of nerve cells that spreads on the surface of the cerebrum, and controls the higher-order functions of the brain such as perception, voluntary movement, thought, reasoning, and memory. On the other hand, the thalamus is a part that occupies a part of the diencephalon, and plays an important role in relaying sensory inputs such as vision, hearing, and somatic sensation to the cerebral neocortex, excluding the sense of smell.
外界からの刺激を大脳皮質に伝える最も主要な経路である視床−皮質軸索の発達、大脳皮質の発達、感覚野の機能に影響する薬剤や遺伝子の探索や評価には、従来、視床−皮質軸索、大脳皮質領域、あるいは、層特異的マーカーを用いた免疫組織化学などの方法が用いられてきた(非特許文献1)。本方法は、切片作製や染色を必要としないことから、個体での解析、サンプル調製(例えば領域特異的DNA、RNA、蛋白質などの調製)に適している。
また、視床−皮質軸索の発達の評価には、従来、トレーサー注入あるいは電気穿孔法やウイルスを用いた遺伝子導入により軸索を標識すること、あるいは、視床-皮質軸索特異的マーカーによる免疫組織化学の手法による標識が行われてきた(非特許文献2)。
The thalamus-cortex has traditionally been used to search for and evaluate drugs and genes that affect thalamic-cortical axon development, cerebral cortex development, and sensory cortex function, the most important route for transmitting external stimuli to the cerebral cortex. Methods such as immunohistochemistry using axons, cerebral cortical regions, or layer-specific markers have been used (Non-Patent Document 1). Since this method does not require section preparation or staining, it is suitable for individual analysis and sample preparation (for example, preparation of region-specific DNA, RNA, protein, etc.).
In addition, for the evaluation of thalamic-cortical axon development, conventionally, axons are labeled by injecting tracer, electroporation or gene introduction using virus, or immune tissue by thalamic-cortical axon specific markers. Labeling by a chemical method has been performed (Non-patent Document 2).
しかしながら、これら従来の方法では、実験ごとのばらつきが大きい、細胞種特異的が得られにくい(トレーサーでは不可能)、技術の習熟が要求される、手術を要するため動物の負担が大きいなどの問題を有していた。 However, with these conventional methods, there are problems such as large variations among experiments, difficulty in obtaining cell type-specificity (impossible with tracers), skill acquisition required, and the burden on animals due to the need for surgery. Had.
従って、本発明の課題は、切片作製や組織学的染色、特殊な技術を必要とすることなく、個体での解析が可能な視床−皮質軸索、大脳皮質の発達、当該発達に影響を及ぼす薬剤や遺伝子の探索及び評価が可能なモデルを提供することにある。 Therefore, the object of the present invention is to influence the development of thalamic-cortical axons and cerebral cortex that can be analyzed in an individual without requiring section preparation, histological staining, or special techniques. The object is to provide a model capable of searching and evaluating drugs and genes.
そこで本発明者は、外界からの刺激を大脳に伝える最も主要な経路である視床−皮質軸索を選択的に標識する手段を開発すべく検討したところ、大腸菌由来人工染色体であるBACクローン上のセロトニントランスポーターのプロモーターの下流に膜移行性シグナル遺伝子とEGFP遺伝子の融合体を挿入したBACクローンを作製し、これを受精卵にマイクロインジェクションすることにより、視床−皮質軸索において選択的にEGFPが発現するトランスジェニックマウスが得られ、当該トランスジェニックマウスは視床−皮質軸索が蛍光標識できるため、視床−皮質軸索の発達及び大脳皮質の発達状態が経時的に解析可能であることを見出し、本発明を完成した。 Therefore, the present inventor studied to develop a means for selectively labeling the thalamic-cortical axon, which is the most important route for transmitting stimuli from the outside world to the cerebrum. A BAC clone in which a fusion protein of membrane translocation signal gene and EGFP gene is inserted downstream of the promoter of serotonin transporter is prepared, and this is microinjected into a fertilized egg, so that EGFP is selectively expressed in thalamic-cortical axons. A transgenic mouse to be expressed is obtained, and the transgenic mouse can fluorescently label the thalamus-cortical axon, and thus it has been found that the development of the thalamus-cortical axon and the developmental state of the cerebral cortex can be analyzed over time, The present invention has been completed.
すなわち、本発明は、以下の〔1〕〜〔7〕を提供するものである。
〔1〕視床−皮質軸索において、セロトニントランスポーターのプロモーター制御下で膜移行型EGFPを発現するトランスジェニックマウス。
〔2〕大腸菌由来人工染色体クローン上のセロトニントランスポーター遺伝子のプロモーターの下流に膜移行性シグナル遺伝子とEGFP遺伝子の融合体を挿入したクローンを導入したものである〔1〕記載のトランスジェニックマウス。
〔3〕膜移行性シグナル遺伝子が、GAP43遺伝子である〔2〕記載のトランスジェニックマウス。
〔4〕大腸菌由来人工染色体クローンが、RP23−39F11クローンである〔2〕又は〔3〕記載のトランスジェニックマウス。
〔5〕受精卵に、大腸菌由来人工染色体クローン上のセロトニントランスポーター遺伝子のプロモーターの下流に膜移行性シグナル遺伝子とEGFP遺伝子の融合体を挿入したクローンを導入することを特徴とする〔1〕記載のトランスジェニックマウスの作製方法。
〔6〕膜移行性シグナル遺伝子が、GAP43遺伝子である〔5〕記載のトランスジェニックマウスの作製方法。
〔7〕大腸菌由来人工染色体クローンが、RP23−39F11クローンである〔5〕又は〔6〕記載のトランスジェニックマウスの作製方法。
That is, the present invention provides the following [1] to [7].
[1] A transgenic mouse that expresses transmembrane EGFP in the thalamus-cortical axon under the control of a serotonin transporter promoter.
[2] The transgenic mouse according to [1], wherein a clone in which a fusion protein of a membrane translocation signal gene and an EGFP gene is inserted downstream of a promoter of a serotonin transporter gene on an Escherichia coli-derived artificial chromosome clone is introduced.
[3] The transgenic mouse according to [2], wherein the membrane translocation signal gene is a GAP43 gene.
[4] The transgenic mouse according to [2] or [3], wherein the E. coli-derived artificial chromosome clone is an RP23-39F11 clone.
[5] The clone according to [1], wherein a clone in which a fusion protein of a membrane translocation signal gene and an EGFP gene is inserted downstream of a promoter of a serotonin transporter gene on an E. coli-derived artificial chromosome clone is introduced into a fertilized egg. Of producing a transgenic mouse.
[6] The method for producing a transgenic mouse according to [5], wherein the membrane translocation signal gene is a GAP43 gene.
[7] The method for producing a transgenic mouse according to [5] or [6], wherein the E. coli-derived artificial chromosome clone is an RP23-39F11 clone.
本発明のトランスジェニックマウスは、発達期の感覚系の視床神経核及びセロトニン神経で発現する遺伝子であるセロトニントランスポーターのプロモーターの制御下でEGFPが発現するため、視床−皮質軸索、及び大脳皮質の領野(感覚野)や層構造(第4層と第6層)を蛍光標識できることから、大脳皮質の領野や層の形成の評価に適している。また、切片作製や組織学的染色を必要とせず生体で体性感覚野、視覚野、聴覚野を明るく蛍光標識できることから、感覚野からのサンプル調製(DNA,RNA,蛋白質)にも適している。 Since the transgenic mouse of the present invention expresses EGFP under the control of the promoter of the serotonin transporter, which is a gene expressed in the thalamic nucleus and the serotonin nerve of the developing sensory system, the thalamus-cortical axon and cerebral cortex Can be fluorescently labeled, and is therefore suitable for evaluating the formation of cortex areas and layers. In addition, the somatosensory area, visual cortex, and auditory cortex can be brightly fluorescently labeled in vivo without the need for section preparation or histological staining, making it suitable for sample preparation (DNA, RNA, protein) from the sensory cortex. .
本発明のトランスジェニックマウスは、視床−皮質軸索において、セロトニントランスポーターのプロモーターの制御下で膜移行型EGFPを発現するマウスである。当該マウスと同様の性質をもったマウスは、マウスの受精卵に、大腸菌由来人工染色体(BAC)クローンのセロトニントランスポーター遺伝子のプロモーターの下流に膜移行性シグナル遺伝子とEGFP遺伝子の融合体を挿入したクローンを導入することにより作製することができる。 The transgenic mouse of the present invention is a mouse that expresses transmembrane EGFP in the thalamus-cortex axon under the control of the promoter of the serotonin transporter. A mouse having the same properties as the mouse inserted a fusion protein of a membrane translocation signal gene and an EGFP gene downstream of the promoter of the serotonin transporter gene of an artificial chromosome (BAC) clone derived from E. coli. It can be prepared by introducing a clone.
マウスとしては、特に制限はなく、通常実験動物として使用される系統のマウスであればよい。 The mouse is not particularly limited and may be a mouse of a strain usually used as an experimental animal.
BACクローンとしては、RP23−39F11を用いるのが好ましい。 RP23-39F11 is preferably used as the BAC clone.
BACクローンに導入する遺伝子は、膜移行性シグナル遺伝子及びEGFP遺伝子の融合体である。膜移行性シグナル遺伝子としては、GAP43遺伝子が好ましい。GAP43遺伝子とEGFP遺伝子を連結して、BACクローンに導入する。 The gene introduced into the BAC clone is a fusion of a membrane translocation signal gene and an EGFP gene. The membrane translocation signal gene is preferably the GAP43 gene. The GAP43 gene and the EGFP gene are ligated and introduced into the BAC clone.
GAP43遺伝子とEGFP遺伝子を挿入する部位は、セロトニントランスポーターの翻訳開始点付近である。セロトニントランスポーターは、発達期の感覚系の視床神経核及びセロトニン神経で発現するため、この遺伝子のプロモーター制御下に膜移行型EGFP遺伝子を挿入すれば、視床−皮質軸索で発現する。 The site where the GAP43 gene and the EGFP gene are inserted is near the translation start point of the serotonin transporter. Since the serotonin transporter is expressed in the thalamic nucleus and the serotonergic nerve of the developing sensory system, if the transmembrane EGFP gene is inserted under the promoter control of this gene, it is expressed in the thalamic-cortical axon.
得られた組み換えBACを、大腸菌中で増幅し、得られたBACクローンを線状化しマウスの受精卵にマイクロインジェクションする。当該受精卵を雌マウスの子宮に着床させ、出生させれば、目的のトランスジェニックマウスが得られる。
得られたトランスジェニックマウスを交配させれば、次世代でヘテロ接合型マウス及びホモ接合型マウスを作製することができる。
The obtained recombinant BAC is amplified in E. coli, and the obtained BAC clone is linearized and microinjected into a fertilized egg of a mouse. If the fertilized egg is implanted into the uterus of a female mouse and born, the desired transgenic mouse can be obtained.
By mating the resulting transgenic mice, heterozygous mice and homozygous mice can be produced in the next generation.
得られた本発明のトランスジェニックマウスは、生後から大脳皮質の発達に伴い、視床−皮質軸索にEGFPが発現し、視床−皮質軸索、大脳皮質が蛍光標識されるので、大脳皮質発達状態、層構造の発達、感覚野の機能等が評価できる。また、種々の薬剤及び遺伝子の視床−皮質軸索、大脳皮質の発達に対する影響も評価できる。また、必要に応じて、大脳皮質の発達段階の蛍光識別組織切片も作用可能である。 The resulting transgenic mouse of the present invention develops cerebral cortex after birth, and EGFP is expressed in the thalamus-cortical axon and the thalamus-cortical axon and cerebral cortex are fluorescently labeled. Evaluation of layer structure development, sensory cortex function, etc. The effects of various drugs and genes on thalamic-cortical axon and cerebral cortex development can also be evaluated. If necessary, a fluorescence distinguishing tissue section at the developmental stage of the cerebral cortex can also act.
次に実施例を挙げて本発明を詳細に説明する。 EXAMPLES Next, an Example is given and this invention is demonstrated in detail.
実施例1
図1のように、トランスジェニックコンストラクトは、B6マウスゲノム由来BACクローンRP23−39F11の改変により作成した。膜移行GAP43シグナル配列(Moriyoshi et al., Neuron 1996(2); 255-260)は2つの一本鎖DNA(F−GAP、R−GAP)のアニーリングにより作成した。開始コドン削除EGFPをF−EGFPとR−EGFPのプライマー対を用いてpEGF−N1(クロンテック社)から増幅した。増幅物は、pEGFP−N1ベクターのNhe/BamHIサイトとBamHI/NotIを連結した。得られたベクター中のGAP43−EGFP−pA配列を、AseI/AftIIで切除し、平滑末端ライゲーションでpS120ベクターのSpeIサイトに挿入した。得られたGAP43−EGFP−pA−Amp−FRT配列をF−カセット及びR−カセットプライマーペアで増幅し、Red/ETシステムでBAC組み換えを行った。BACコンストラクト中のFRT−Amp−FRT配列を大腸菌中のflp/FRY組み換えで削除した。トランスジェニックファウンダーマウスは鎖状DNAコンストラクトのB6マウス受精卵へのマイクロインジェクションにより作成した。得られた受精卵を雌マウスの子宮に導入して、出産させてトランスジェニックマウスを作製した。
Example 1
As shown in FIG. 1, the transgenic construct was prepared by modifying the BAC mouse genome-derived BAC clone RP23-39F11. The membrane translocation GAP43 signal sequence (Moriyoshi et al., Neuron 1996 (2); 255-260) was generated by annealing two single-stranded DNAs (F-GAP, R-GAP). The start codon deleted EGFP was amplified from pEGF-N1 (Clontech) using a primer pair of F-EGFP and R-EGFP. The amplified product was obtained by linking the Nhe / BamHI site of the pEGFP-N1 vector and BamHI / NotI. The GAP43-EGFP-pA sequence in the obtained vector was excised with AseI / AftII and inserted into the SpeI site of the pS120 vector by blunt end ligation. The obtained GAP43-EGFP-pA-Amp-FRT sequence was amplified with the F-cassette and R-cassette primer pair, and BAC recombination was performed with the Red / ET system. The FRT-Amp-FRT sequence in the BAC construct was deleted by flp / FRY recombination in E. coli. Transgenic founder mice were prepared by microinjection of a strand DNA construct into B6 mouse fertilized eggs. The resulting fertilized egg was introduced into the uterus of a female mouse and allowed to give birth to produce a transgenic mouse.
得られたマウスラインのうちライン♯40では、出生直後において、一次感覚野および一次感覚野に対応する視床核に限局した強いEGFPの発現が認められた(図2B、図2C)。このマウスラインでは、切片を作製することなしにバレル地図の観察を行うことが可能であった(図2)。 In line # 40 of the obtained mouse lines, immediately after birth, strong EGFP expression limited to the primary sensory cortex and the thalamic nucleus corresponding to the primary sensory cortex was observed (FIGS. 2B and 2C). With this mouse line, it was possible to observe a barrel map without preparing a section (FIG. 2).
実施例2
得られたトランスジェニックマウスの出生2〜16日後の大脳皮質蛍光像を示す(図3)。図3より、大脳皮質の層形成が明確に観察できる。
Example 2
The cerebral cortex fluorescence image 2 to 16 days after birth of the obtained transgenic mouse is shown (FIG. 3). From FIG. 3, cerebral cortex layer formation can be clearly observed.
実施例3
生後7日齢のトランスジェニックマウスの脳切片標本を図4に示す。図4より、EGFPが感覚系視床神経核(LGN,VPM,VPL)から大脳皮質(Cx)に伸びる軸索上に発現していることがわかる。
Example 3
FIG. 4 shows a brain section sample of a 7-day-old transgenic mouse. FIG. 4 shows that EGFP is expressed on axons extending from the sensory system thalamic nucleus (LGN, VPM, VPL) to the cerebral cortex (Cx).
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JP2006511197A (en) * | 2002-05-31 | 2006-04-06 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Heterogeneous stimulus-gated ion channel and method of use thereof |
JP2011515076A (en) * | 2008-02-28 | 2011-05-19 | ユニバーシティ オブ バージニア パテント ファウンデーション | Serotonin transporter gene and treatment of alcoholism |
-
2014
- 2014-03-04 JP JP2014041326A patent/JP2015165780A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006511197A (en) * | 2002-05-31 | 2006-04-06 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Heterogeneous stimulus-gated ion channel and method of use thereof |
JP2011515076A (en) * | 2008-02-28 | 2011-05-19 | ユニバーシティ オブ バージニア パテント ファウンデーション | Serotonin transporter gene and treatment of alcoholism |
Non-Patent Citations (3)
Title |
---|
GENOME RESEARCH, 2000, VOL.10, P.116-128, JPN6017028345 * |
MUTANT MOUSE RESOURCE & RESEARCH CENTER, MMRRC:030692-UCD, [ONLINE], [平成29年7月21日検索],, JPN6017028346 * |
NATURE, 2003, VOL.425, P.917-925, SUPPLEMENTAL TABLE 1, JPN6017028344 * |
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