Trial research of fibrous dysplasia model transplanted with GNAS1 mutant cells

GNAS1突变细胞移植纤维异常增殖症模型的试验研究

• 批准号: 23659877
• 负责人: TOYOSAWA Satoru
• 金额: $ 2.25万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659877/
• 关键词: 線維性骨異形成症; GNAS1遺伝子; 骨髄間質細胞; 遺伝子診断; 同所性移植; マウスモデル

To replacement Arg201 with His in the Gs, we produced mutated GNAS1 gene (R201H) replacing with A instead of G of the human GNAS1 gene, which causes human fibrous dysplasia of bone (FD). To stably transfer the R201H into cultured cells, we constructed a lentiviral vector expressing R201H, and used it to transduce C57BL/6 mice-derived marrow stromal cells. We are now elucidating the cell proliferation and differentiation of the R201H-expressing cells and are going to make a mouse model by the orthotopic transplant of the transduced cells. In addition, we studied the method of highly precise genetic tests that we could distinguish it from other similar bone lesions. As a result, the real-time PCR using PNA probe and pyrosequencing method were more effective, compared to conventional PCR-restriction fragment length polymorphism.

用GS中的Arg201取代Arg201，我们产生了突变的GNAS1基因（R201H），用a而不是人类GNAS1基因代替，这会导致人类的骨骼纤维纤维发育异常（FD）。为了稳定地将R201H转移到培养的细胞中，我们构建了表达R201H的慢病毒载体，并将其用于传递C57BL/6小鼠衍生的Marrow Stromal细胞。现在，我们正在阐明表达R201H的细胞的细胞增殖和分化，并将通过转导细胞的原位移植来形成小鼠模型。此外，我们研究了高度精确的基因检测方法，我们可以将其与其他类似的骨病变区分开。结果，与常规的PCR限制片段长度多态性相比，使用PNA探针和焦磷酸测序方法的实时PCR更有效。

项目成果

ビスフォスフォネート関連顎骨壊死の病態を考える

考虑双膦酸盐相关颌骨坏死的病理学

• 发表时间: 2012
• 作者: Takashi Izawa;Tomoyuki Kondo;Mie Kurosawa;Ritsuko Oura;Kazuma Matsumoto;Eiji Tanaka;Akiko Yamada;Rieko Arakaki;Yasusei Kudo;Yoshio Hayashi and Naozumi Ishimaru;豊澤 悟
• 通讯作者: 豊澤 悟

リウマチ病セミナーXXIII:Fibrous dysplasia 再訪

风湿病研讨会二十三：纤维异常增殖症重温

• 发表时间: 2012
• 作者: 豊澤 悟;岸野万伸;佐藤 淳;他
• 通讯作者: 他

Fibrous dysplasia 再訪

纤维发育不良的再探讨

• 发表时间: 2011
• 作者: Hirai Kimito;Maeda Hiroshi;Omori Kazuhiro;Yamamoto Tadashi;Kokegichi Susumu;Takashiba Shogo;豊澤 悟
• 通讯作者: 豊澤 悟

Loss of B-catenin induces multifocal periosteal chondroma-like masses in mice.

B-连环蛋白的缺失会导致小鼠出现多灶性骨膜软骨瘤样肿块。

• 发表时间: 2013
• 期刊: Am J Pathol
• 影响因子: 6
• 作者: Cantley L;Saunders C;Guttenberg M;Candela ME;Ohta Y;Yasuhara R;Kondo N;Sgariglia F;Asai S;Zhang X;Qin L;Hecht JT;Chen D;Yamamoto M;Toyosawa S;Dormans JP;Esko JD;Yamaguchi Y;Iwamoto M;Pacifici M;Enomoto-Iwamoto M
• 通讯作者: Enomoto-Iwamoto M

顎骨の線維ー骨性病変 -歯原性腫瘍との鑑別点を含めて-

颌骨纤维骨病变 - 包括与牙源性肿瘤的鉴别点 -

• 发表时间: 2013
• 期刊: 病理と臨床
• 作者: Cantley L;Saunders C;Guttenberg M;Candela ME;Ohta Y;Yasuhara R;Kondo N;Sgariglia F;Asai S;Zhang X;Qin L;Hecht JT;Chen D;Yamamoto M;Toyosawa S;Dormans JP;Esko JD;Yamaguchi Y;Iwamoto M;Pacifici M;Enomoto-Iwamoto M;豊澤 悟
• 通讯作者: 豊澤 悟