Expression of stabilized beta-catenin in differentiated neurons of transgenic mice does not result in tumor formation.
Expression of stabilized beta-catenin in differentiated neurons of transgenic mice does not result in tumor formation.
复制标题
转基因小鼠分化神经元中稳定β-catenin的表达不会导致肿瘤形成。
DOI：
10.1186/1471-2407-2-33
复制
发表时间：
2002-12-02
期刊：
影响因子：
3.8
通讯作者：
Eberhart, CG
中科院分区：
文献类型：
--
作者：
Kratz, JE;Stearns, D;Huso, DL;Slunt, HH;Price, DL;Borchelt, DR;Eberhart, CG
成神经管细胞瘤是发生在小脑的胚胎性肿瘤，通常含有激活Wnt信号的突变。为了确定成年CNS中增加的Wnt信号传导是否足以诱导肿瘤形成，我们创建了在脑中表达野生型或活化的β-连环蛋白的转基因小鼠。野生型和突变型人β-连环蛋白转基因在鼠PrP启动子片段的控制下表达，该启动子片段驱动CNS中的高水平出生后表达。突变的β-连环蛋白通过密码子37中丝氨酸至苯丙氨酸的改变而稳定。突变转基因的表达导致成年动物皮质和小脑中β-连环蛋白蛋白水平增加约两倍。免疫组织化学分析显示，在转基因动物的海马、皮质和小脑神经元中存在核β-连环蛋白，但在非转基因对照中没有。在一些转基因动物中观察到尾部扭结，但未检测到CNS畸形或肿瘤。在表达稳定的β-连环蛋白的转基因小鼠的脑中未检测到肿瘤或形态学改变，表明分化神经元中的出生后Wnt信号传导可能不足以诱导CNS肿瘤发生。
Medulloblastomas, embryonal tumors arising in the cerebellum, commonly contain mutations that activate Wnt signaling. To determine whether increased Wnt signaling in the adult CNS is sufficient to induce tumor formation, we created transgenic mice expressing either wild-type or activated β-catenin in the brain. Wild-type and mutant human β-catenin transgenes were expressed under the control of a murine PrP promoter fragment that drives high level postnatal expression in the CNS. Mutant β-catenin was stabilized by a serine to phenylalanine alteration in codon 37. Expression of the mutant transgene resulted in an approximately two-fold increase in β-catenin protein levels in the cortex and cerebellum of adult animals. Immunohistochemical analysis revealed nuclear β-catenin in hippocampal, cortical and cerebellar neurons of transgenic animals but not in non-transgenic controls. Tail kinking was observed in some transgenic animals, but no CNS malformations or tumors were detected. No tumors or morphologic alterations were detected in the brains of transgenic mice expressing stabilized β-catenin, suggesting that postnatal Wnt signaling in differentiated neurons may not be sufficient to induce CNS tumorigenesis.
登录
查看更多内容
DOI：
10.1016/s1050-3862(96)00167-2
发表时间：
1996-12-01
期刊：
GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING
影响因子：
--
作者：
Borchelt, DR;Davis, J;Price, DL
通讯作者：
Price, DL
影响因子：
4.8
作者：
RAFFEL, C;THOMAS, GA;RUTKA, JT
通讯作者：
RUTKA, JT
影响因子：
--
作者：
Barel, D;Avigad, S;Zaizov, R
通讯作者：
Zaizov, R
影响因子：
4.8
作者：
Fults, D;Pedone, C;Holland, EC
通讯作者：
Holland, EC
DOI：
10.1073/pnas.012414099
发表时间：
2002-01-08
影响因子：
11.1
作者：
Miyoshi, K;Shillingford, JM;Khazaie, K
通讯作者：
Khazaie, K